Cyclodextrin-Based Microemulsions, and Dermatological Uses Thereof

ABSTRACT

Described herein are cyclodextrin-stabilized microemulsion systems useful for increasing the solubility, stability, bioavailability, or safety of an active agent for delivery to the skin. The microemulsions may reduce the occurrence of skin irritation or odor upon application. In certain embodiments, the active agent is substantially insoluble in water.

RELATED APPLICATIONS

This application claims the benefit of priority to U.S. ProvisionalPatent Application Ser. No. 61/614,177, filed Mar. 22, 2012, thecontents of which are hereby incorporated by reference.

BACKGROUND

Microemulsions are thermodynamically-stable, optically-clear emulsionshaving submicron-sized droplets suspended in a continuous phase. Theseemulsions form spontaneously, and typically consist of an aqueous phase,an organic phase, and a surfactant/co-surfactant component.

Previous data suggest that volatile lower alcohols, such as ethanol, arerequired to maintain stable oil-in-water microemulsions. However,topical application of volatile lower alcohols has a drying effect onthe skin. Additionally, volatile lower alcohols and compositionscontaining them are extremely flammable. For these reasons, volatilelower alcohol-containing microemulsions for topical application haveseen limited commercial use.

Developing a formulation for a water-immiscible drug that displaysdesirable drug delivery and solubilization characteristics while meetingother formulation criteria, such as targeted drug concentration, drugstability, bioavailability, safety, and others, is challenging.Currently, many drug delivery systems are available, includingliposomes, polymeric/surfactant aggregates, microemulsions. However,these systems have numerous shortcomings, such as low efficiency (e.g.,low bioavailability of drug), heterogeneity, and instability of thedelivery systems themselves.

There exists a need for a drug delivery vehicle for topicaladministration wherein a water-immiscible drug may be encapsulated orsolublilized.

SUMMARY OF THE INVENTION

In certain embodiments, the invention relates to an activeagent-containing microemulsion consisting essentially of an active agentand a microemulsion, wherein the microemulsion consists essentially ofan aqueous phase, a first surfactant, and a second surfactant; and thefirst surfactant is a cyclodextrin or a derivative of a cyclodextrin.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 depicts a schematic of an example of an oil-in-watermicroemulsion with cyclodextrin and drug molecules.

FIG. 2 depicts ternary phase diagrams developed from systems withLabrasol® (caprylocaproyl macrogol-8 glycerides and/or caprylocaproylpolyoxyl-8 glycerides), hydroxypropyl X-cyclodextrin (where X=alpha,beta, or gamma, HPXCD), and pure water. The shaded portions indicate theexistence of micro emulsions.

FIG. 3 depicts ternary phase diagrams of systems containing (1) aqueousphase (squares, see FIG. 5 for compositions); and (2) pure water (blackcircles). The shaded portions of (a) indicate the existence of amicroemulsion.

FIG. 4( a) depicts a Labrasol®-HPGCD-water microemulsion system, whichis transparent, containing retinol (from Retistar) in a finalconcentration of 0.06%. This microemulsion also contains capric/caprylictriglycerides.

FIG. 4( b) depicts a Labrasol®-HPGCD-water microemulsion system, whichis transparent, containing retinol (from Retinol 50C) in a finalconcentration of 1.2%. This microemulsion also contains capric/caprylictriglycerides. The miscibility of retinol in this composition may beattributed to either or both of the cyclodextrin system and themicroemulsion system.

FIG. 4( c) depicts a Labrasol®-HPGCD-water microemulsion system, whichis transparent, containing solid retinol in a final concentration of1.2%. The miscibility of retinol in this composition may be attributedto either or both of the cyclodextrin system and the microemulsionsystem.

FIG. 5 tabulates the composition of a representative aqueous phase.

FIG. 6 tabulates the compositions of (a) a microemulsion of theinvention (microemulsion A); and (b) a second microemulsion of theinvention (microemulsion B).

FIG. 7 depicts (top row, left to right, final retinolconcentration=0.06%) 1.2% Retistar in water (F); 1.2% Retistar in waterwith 5% HPACD (G); 1.2% Retistar in water with 15% Labrasol® and 5%HPACD (H); 1.2% Retistar in water (B); 1.2% Retistar in water with 5%HPBCD (C); 1.2% Retistar in water with 15% Labrasol® and 5% HPBCD (D);1.2% Retistar in water (J); 1.2% Retistar in water with 5% HPGCD (K);1.2% Retistar in water with 15% Labrasol® and 5% HPGCD (L); and (bottomrow, left to right, final retinol concentration=1.2%) 2.66% Retinol 50Cin water (2); 2.66% Retinol 50C in water with 5% HPACD (3); 2.66%Retinol 50C in water with 15% Labrasol® and 5% HPACD (4); 2.66% Retinol50C in water (6); 2.66% Retinol 50C in water with 5% HPGCD (7); 2.66%Retinol 50C in water with 15% Labrasol® and 5% HPGCD (8); and 1.2% solidretinol in water with 15% Labrasol® and 5% HPGCD (1).

FIG. 8 depicts a ternary phase diagram developed from systems withLabrasol®, HPBCD, and aqueous phase (see FIG. 10 for composition). Theshaded portions indicate the existence of micro emulsions.

FIG. 9 depicts a ternary phase diagram developed from systems withLabrasol®, HPBCD, and (1) aqueous phase (squares, see FIG. 10 forcomposition) or (2) pure water (black circles).

FIG. 10 tabulates the components and weight percentage of each componentin an exemplary cream formulation.

FIG. 11 depicts the compatibility of the microemulsion (bottom phase ofeach picture; 1.2% retinol in Labrasol®-HPGCD-aqueous solution, 80:5:15)with the oil that may be present in the oil phase of a cream formulation(top phase of each picture; 1=light mineral oil; 2=isononylisononanoate; 3=silicon oil; and 4=isopropyl myristate).

FIG. 12 depicts (left) a finished cream product containing 0.5% retinolencapsulated in a HPGCD-based microemulsion base; and (right) acorresponding control (0.5% retinol product without microemulsion).

FIG. 13 tabulates the components and the weight percentage of eachcomponent in an exemplary cream formulation, which uses aretinol-transforming treatment vehicle.

FIG. 14 tabulates the components and the weight percentage of eachcomponent in an exemplary cream formulation, which comprises retinol asthe active agent.

FIG. 15 tabulates the components and the weight percentage of eachcomponent of a microemulsion-based gel formulation (using retinol as theactive agent).

FIG. 16 tabulates the results from chemical stability testing for 2weeks at 40° C. for compositions with and without the microemulsioninvention.

DETAILED DESCRIPTION OF THE INVENTION Overview

In certain embodiments, the invention relates to the use ofcyclodextrins (CDs) as a co-surfactant in microemulsion formulationsfree of volatile lower alcohols.

In certain embodiments, the invention relates to cyclodextrin-stabilizedmicroemulsion formulations. In certain embodiments, thecyclodextrin-stabilized microemulsion formulations display desirableproperties, such as increased drug solubility, stability,bioavailability, safety, reduced skin irritation, and the ability tomask odors.

In certain embodiments, the invention relates to any one of theaforementioned microemulsions, wherein the microemulsion does notcomprise methanol, ethanol, propanol, or butanol.

In certain embodiments, the active agent-containing microemulsionformulation, upon mixing with a propellant in a pressurized container,remains a single-phase, optically-clear microemulsion. In certainembodiments, upon actuation from an aerosol container, microemulsionformulations of the present invention produce foam.

CD-Stabilized Microemulsions

In certain embodiments, the invention relates to a surfactantcombination in aqueous solution that displays phase behaviorcharacteristic of microemulsions, i.e., spontaneous formation ofoptically clear solutions when mixed in the proper ratios. While it hasbeen reported that cyclodextrins are able to stabilize conventionaloil-in-water emulsions, there have been no reports of cyclodextrinsserving as co-surfactants stabilizing microemulsions. In certainembodiments, conventional oil-in-water emulsions and microemulsions aresimilar in that they both consist of oil droplets dispersed in anaqueous phase. However they exhibit specific and fundamentaldifferences. First, the oil droplet size in a microemulsion is one ormore orders of magnitude smaller than the smallest droplet sizeachievable in a conventional emulsion. Second, conventional emulsionsare thermodynamically unstable and require significant energy input tobe created; in contrast microemulsions are thermodynamically stable andcan form spontaneously with minimal mixing.

In certain embodiments, studies of the phase behavior of acaprylocaproyl polyethylene glycol surfactant/cyclodextrin/water systemdemonstrated the characteristic phase behavior properties of amicroemulsion (FIGS. 1-4). In certain embodiments, the microemulsions ofthe invention also satisfy the physical characteristics of a typicalmicroemulsion systems like: spontaneous formation, a clear isotopicsolution, stability, or others. In certain embodiments, areas under thecurve (FIG. 2, lined) represent the clear/single phase microemulsionsystems. In certain embodiments, compositions outside the phase boundarylines are opaque/heterogeneous emulsion systems. In certain embodiments,much like established microemulsion systems, the inventive microemulsionsystems required minimal shaking (simple vortexing or manual shaking)for formation and remained stable when thermodynamically controlled.From the phase diagram, it is hypothesized that the total area coveringthe clear phase, i.e., the microemulsion zone, increases as the corediameter of the cyclodextrin increases (i.e., HPACD<HPBCD<HPGCD). Incertain embodiments, caprylocaproyl macrogol-8 glycerides and/orcaprylocaproyl polyoxyl-8 glycerides (Labrasol®), an oily liquid withamphiphilic properties and dispersible in water, is treated as an oil inthis Labrasol®-HPXCD-water systems. In certain embodiments, appropriatequantities of other oily/amphiphilic solvent(s)/surfactant(s) (e.g.,caprylic/capric triglyceride, Spans, Tween, isopropyl myristate, oleicacid, diethyl sebacate, transcutol, etc.) can be added to these systemswhile maintaining the integrity of the microemulsion. In certainembodiments, additional co-solvents (e.g., propylene glycol, ethanol,hexylene glycol) or the ingredients (e.g., urea, salt, sorbitol) may beadded to see the effect of the microemulsion phase boundary lines andhence the drug solubility (when applicable) in the reported systems.

Encapsulation of Active Agents in CD-Stabilized Microemulsions

In certain embodiments, a microemulsion as described herein may beuseful in delivering water-immiscible ingredients. In certainembodiments, a model drug is retinol. Retinol is immiscible in water andcommercially available as a dispersion in oil or surfactant medium(e.g., Retistar® and Retinol 50 C, respectively). Solid Retinol is alsocommercially available, but requires very low temperature storageconditions to avoid physical and chemical instability. In certainembodiments, using the cyclodextrin-based microemulsions of theinvention, it is possible to incorporate into the systems greater than1.0 wt % of retinol. In certain embodiments, the cyclodextrin-basedmicroemulsion systems allow retinol to be sheltered inside the core ofthe cyclodextrin, as well as inside the microemulsion core. In certainembodiments, and not wishing to be bound by any particular theory, thedual-shelter structure may increase the thermodynamic activity of thedrug molecules, and thus enhance drug release from vehicles(bioavailability). In certain embodiments, the encapsulation of a drugusing the above method can be used to address a drug's solubility orstability, to enhance bioavailability, to reduce skin irritation, toincrease safety, or to mask odors. In certain embodiments, otherwater-immiscible drugs or cosmetic ingredients can benefit from thissystem. In certain embodiments, molecules that may benefit from thissystem include, but are not limited to, Retinol, Colchicine, Benzoylperoxide, Hydroquinone, Tretinoin, Clobetasol propionate, and Adapalene.

In certain embodiments, the drug encapsulation method is useful for thedelivery of other water-immiscible drugs using topical (for example,dermal or transdermal), parental, ocular, nasal, rectal, or other routesof drug delivery. In certain embodiments, the systems can be used forcontrolled drug delivery using the advantage of simultaneous drugencapsulation in two different systems (i.e., microemulsion andcyclodextrin).

Semi-Solid and Foam Formulations Containing CD-Stabilized Microemulsionsof Active Agents

In certain embodiments, the invention relates to a method of formulatinga semi-solid cyclodextrin-based microemulsion system, wherein thecyclodextrin-based microemulsion comprises an encapsulatedwater-immiscible drug. In certain embodiments, the invention relates toa method of increasing drug loading in a semi-solid or foam formulationby using the cyclodextrin-based microemulsion system.

In certain embodiments, the invention relates to a cream or lotionformulation comprising a cyclodextrin-based microemulsion system. Incertain embodiments, the invention relates to a method of making thecream or lotion formulation. In certain embodiments, the cream or lotionformulation is useful for topical and other applications. In certainembodiments, the cyclodextrin-based microemulsion system comprises theaqueous phase of the cream/lotion. In certain embodiments, the oil phaseof the cream/lotion, is immiscible with the microemulsion system. Incertain embodiments, the cream may be thickened using oil or awater-miscible thickener that does not destabilize the microemulsion. Incertain embodiments, additional loading of the drug is possible when thethickener is selected from the group consisting of chitosan, sodiumalginate, and block copolymers that also have ability to solubilize thedrug.

In certain embodiments, the invention relates to an aerosol foamformulation comprising a cyclodextrin-based microemulsion system. Incertain embodiments, the aerosol foam formulation comprises theaforementioned cream formulation and a propellant.

In certain embodiments, the invention relates to a non-aerosol foamformulation comprising a cyclodextrin-based microemulsion system. Incertain embodiments, additional surfactant or foam boasting ingredientmay be added (to achieve the desired foam quality) as long as themicroemulsion remains intact.

DEFINITIONS

For convenience, certain terms employed in the specification andappended claims are collected here. These definitions should be read inlight of the entire disclosure and understood as by a person of skill inthe art.

The indefinite articles “a” and “an,” as used herein in thespecification and in the claims, unless clearly indicated to thecontrary, should be understood to mean “at least one.”

The phrase “and/or,” as used herein in the specification and in theclaims, should be understood to mean “either or both” of the elements soconjoined, i.e., elements that are conjunctively present in some casesand disjunctively present in other cases. Multiple elements listed with“and/or” should be construed in the same fashion, i.e., “one or more” ofthe elements so conjoined. Other elements may optionally be presentother than the elements specifically identified by the “and/or” clause,whether related or unrelated to those elements specifically identified.Thus, as a non-limiting example, a reference to “A and/or B”, when usedin conjunction with open-ended language such as “comprising” can refer,in one embodiment, to A only (optionally including elements other thanB); in another embodiment, to B only (optionally including elementsother than A); in yet another embodiment, to both A and B (optionallyincluding other elements); etc.

The phrase “or,” as used herein in the specification and in the claims,should be understood to mean “either or both” of the elements soconjoined, i.e., elements that are conjunctively present in some casesand disjunctively present in other cases. Multiple elements listed with“or” should be construed in the same fashion, i.e., “one or more” of theelements so conjoined. Other elements may optionally be present otherthan the elements specifically identified by the “or” clause, whetherrelated or unrelated to those elements specifically identified. Thus, asa non-limiting example, a reference to “A or B”, when used inconjunction with open-ended language such as “comprising” can refer, inone embodiment, to A only (optionally including elements other than B);in another embodiment, to B only (optionally including elements otherthan A); in yet another embodiment, to both A and B (optionallyincluding other elements); etc.

As used herein in the specification and in the claims, the phrase “atleast one,” in reference to a list of one or more elements, should beunderstood to mean at least one element selected from any one or more ofthe elements in the list of elements, but not necessarily including atleast one of each and every element specifically listed within the listof elements and not excluding any combinations of elements in the listof elements. This definition also allows that elements may optionally bepresent other than the elements specifically identified within the listof elements to which the phrase “at least one” refers, whether relatedor unrelated to those elements specifically identified. Thus, as anon-limiting example, “at least one of A and B” (or, equivalently, “atleast one of A or B,” or, equivalently “at least one of A and/or B”) canrefer, in one embodiment, to at least one, optionally including morethan one, A, with no B present (and optionally including elements otherthan B); in another embodiment, to at least one, optionally includingmore than one, B, with no A present (and optionally including elementsother than A); in yet another embodiment, to at least one, optionallyincluding more than one, A, and at least one, optionally including morethan one, B (and optionally including other elements); etc.

It should also be understood that, unless clearly indicated to thecontrary, in any methods claimed herein that include more than one stepor act, the order of the steps or acts of the method is not necessarilylimited to the order in which the steps or acts of the method arerecited.

In the claims, as well as in the specification, all transitional phrasessuch as “comprising,” “including,” “carrying,” “having,” “containing,”“involving,” “holding,” “composed of,” and the like are to be understoodto be open-ended, i.e., to mean including but not limited to. Only thetransitional phrases “consisting of” and “consisting essentially of”shall be closed or semi-closed transitional phrases, respectively, asset forth in the United States Patent Office Manual of Patent ExaminingProcedures, Section 2111.03.

Exemplary Constituents of Emulsions and Compositions of the Invention

Exemplary identities of various constituents of the compositions of thepresent invention are described below.

1. Propellants

In certain embodiments, the propellant is a HFA or a mixture of one ormore hydrofluorocarbons. Suitable hydrofluorocarbons include1,1,1,2-tetrafluoroethane (HFA 134a); 1,1,1,2,3,3,3-heptafluoropropane(HFA 227); and mixtures and admixtures of these and other HFAs that arecurrently approved or may become approved for medical use are suitable.The concentration of the HFA propellant is from about 2% to about 50% byweight of the composition. In certain embodiments, the propellantcomprises a hydrofluoroolefin (HFO), or a mixture of HFO and HFA.Suitable hydrofluoroolefins include 1,3,3,3-tetrafluoropropene (HFO1234ze) and mixtures and admixtures of this and other HFO suitable fortopical use. The concentration of the HFO propellant is from about 2% toabout 50% by weight of the composition. Hydrocarbon as well as CFCpropellants can also be used in the present invention.

2. Vehicles

Suitable topical vehicles and vehicle components for use with theformulations of the invention are well known in the cosmetic andpharmaceutical arts, and include such vehicles (or vehicle components)as water; organic solvents such as alcohols (particularly lower alcoholsreadily capable of evaporating from the skin such as ethanol), glycols(such as propylene glycol, butylene glycol, and glycerol (glycerin)),aliphatic alcohols (such as lanolin); mixtures of water and organicsolvents (such as water and alcohol), and mixtures of organic solventssuch as alcohol and glycerol (optionally also with water); lipid-basedmaterials such as fatty acids, acylglycerols (including oils, such asmineral oil, and fats of natural or synthetic origin),phosphoglycerides, sphingolipids and waxes; protein-based materials suchas collagen and gelatin; silicone-based materials (both non-volatile andvolatile) such as cyclomethicone, dimethiconol, dimethicone, anddimethicone copolyol; hydrocarbon-based materials such as petrolatum andsqualane; and other vehicles and vehicle components that are suitablefor administration to the skin, as well as mixtures of topical vehiclecomponents as identified above or otherwise known to the art.

In one embodiment, the compositions of the present invention areoil-in-water emulsions. Liquids suitable for use in formulatingcompositions of the present invention include water, and water-misciblesolvents such as glycols (e.g., ethylene glycol, butylene glycol,isoprene glycol, propylene glycol), glycerol, liquid polyols, dimethylsulfoxide, and isopropyl alcohol. One or more aqueous vehicles may bepresent.

In one embodiment, formulations without methanol, ethanol, propanols, orbutanols are desirable.

3. Surfactants and Emulsifiers

Many topical formulations contain chemical emulsions which use surfaceactive ingredients (emulsifiers and surfactants) to disperse dissimilarchemicals in a particular solvent system. For example, most lipid-like(oily or fatty) or lipophilic ingredients do not uniformly disperse inaqueous solvents unless they are first combined with emulsifiers, whichform microscopic aqueous soluble structures (droplets) that contain alipophilic interior and a hydrophilic exterior, resulting in anoil-in-water emulsion. In order to be soluble in aqueous media, amolecule must be polar or charged so as to favorably interact with watermolecules, which are also polar. Similarly, to dissolve anaqueous-soluble polar or charged ingredient in a largely lipid oroil-based solvent, an emulsifier is typically used which forms stablestructures that contain the hydrophilic components in the interior ofthe structure while the exterior is lipophilic so that it can dissolvein the lipophilic solvent to form a water-in-oil emulsion. It is wellknown that such emulsions can be destabilized by the addition of saltsor other charged ingredients which can interact with the polar orcharged portions of the emulsifier within an emulsion droplet. Emulsiondestabilization results in the aqueous and lipophilic ingredientsseparating into two layers, potentially destroying the commercial valueof a topical product.

Surfactants suitable for use in the present invention may be ionic ornon-ionic. These include, but are not limited to: cetyl alcohol,polysorbates (Polysorbate 20, Polysorbate 40, Polysorbate 60,Polysorbate 80), steareth-10 (Brij 76), sodium dodecyl sulfate (sodiumlauryl sulfate), lauryl dimethyl amine oxide, cetyltrimethylammoniumbromide (CTAB), polyethoxylated alcohols, polyoxyethylene sorbitan,octoxynol, N,N-dimethyldodecylamine-N-oxide, hexadecyltrimethylammoniumbromide (HTAB), polyoxyl 10 lauryl ether, bile salts (such as sodiumdeoxycholate or sodium cholate), polyoxyl castor oil, nonylphenolethoxylate, cyclodextrins, lecithin, dimethicone copolyol, lauramideDEA, cocamide DEA, cocamide MEA, oleyl betaine, cocamidopropyl betaine,cocamidopropyl phosphatidyl PG-dimonium chloride, dicetyl phosphate(dihexadecyl phosphate), ceteareth-10 phosphate, methylbenzethoniumchloride, dicetyl phosphate, ceteth-10 phosphate (ceteth-10 is thepolyethylene glycol ether of cetyl alcohol where n has an average valueof 10; ceteth-10 phosphate is a mixture of phosphoric acid esters ofceteth-10), ceteth-20, Brij S10 (polyethylene glycol octadecyl ether,average M_(n)˜711), and Poloxamers (including, but not limited to,Poloxamer 188 (HO(C₂H₄O)_(a)(CH(CH₃)CH₂O)_(b)(C₂H₄O)_(a)H, averagemolecular weight 8400) and Poloxamer 407(HO(C₂H₄O)_(a)(CH(CH₃)CH₂O)_(b)(C₂H₄O)_(a)H, wherein a is about 101 andb is about 56)). Appropriate combinations or mixtures of suchsurfactants may also be used according to the present invention.

Many of these surfactants may also serve as emulsifiers in formulationsof the present invention.

Other suitable emulsifiers for use in the formulations of the presentinvention include, but are not limited to, behentrimoniummethosulfate-cetearyl alcohol, non-ionic emulsifiers like emulsifyingwax, polyoxyethylene oleyl ether, PEG-40 stearate, cetostearyl alcohol(cetearyl alcohol), ceteareth-12, ceteareth-20, ceteareth-30, cetearethalcohol, Ceteth-20 (Ceteth-20 is the polyethylene glycol ether of cetylalcohol where n has an average value of 20), oleic acid, oleyl alcohol,glyceryl stearate, PEG-75 stearate, PEG-100 stearate, and PEG-100stearate, ceramide 2, ceramide 3, stearic acid, cholesterol, steareth-2,and steareth-20, or combinations/mixtures thereof, as well as cationicemulsifiers like stearamidopropyl dimethylamine and behentrimoniummethosulfate, or combinations/mixtures thereof

4. Moisturizers, Emollients, and Humectants

One of the most important aspects of topical products in general, andcosmetic products in particular, is the consumer's perception of theaesthetic qualities of a product. For example, while white petrolatum isan excellent moisturizer and skin protectant, it is rarely used alone,especially on the face, because it is greasy, sticky, does not rubeasily into the skin and may soil clothing. Consumers highly valueproducts which are aesthetically elegant and have an acceptable tactilefeel and performance on their skin.

Suitable moisturizers for use in the formulations of the presentinvention include, but are not limited to, lactic acid and other hydroxyacids and their salts, glycerol, propylene glycol, butylene glycol,sodium PCA, sodium hyaluronate, Carbowax 200, Carbowax 400, and Carbowax800.

Suitable emollients or humectants for use in the formulations of thepresent invention include, but are not limited to, panthenol, cetylpalmitate, glycerol (glycerin), PPG-15 stearyl ether, lanolin alcohol,lanolin, lanolin derivatives, cholesterol, petrolatum, isostearylneopentanoate, octyl stearate, mineral oil, isocetyl stearate, myristylmyristate, octyl dodecanol, 2-ethylhexyl palmitate (octyl palmitate),dimethicone, phenyl trimethicone, cyclomethicone, C₁₂-C₁₅ alkylbenzoates, dimethiconol, propylene glycol, Theobroma grandiflorum seedbutter, ceramides (e.g., ceramide 2 or ceramide 3), hydroxypropylbispalmitamide MEA, hydroxypropyl bislauramide MEA, hydroxypropylbisisostearamide MEA, 1,3-bis(N-2-(hydroxyethyl)stearoylamino)-2-hydroxypropane, bis-hydroxyethyl tocopherylsuccinoylamido hydroxypropane, urea,aloe, allantoin, glycyrrhetinic acid, safflower oil, oleyl alcohol,oleic acid, stearic acid, dicaprylate/dicaprate, diethyl sebacate,isostearyl alcohol, pentylene glycol, isononyl isononanoate, and1,3-bis(N-2-(hydroxyethyl)palmitoylamino)-2-hydroxypropane.

In addition, appropriate combinations and mixtures of any of thesemoisturizing agents and emollients may be used in accordance with thepresent invention.

5. Preservatives and Antioxidants

The composition may further include components adapted to improve thestability or effectiveness of the applied formulation.

Suitable preservatives for use in the present invention include, but arenot limited to: ureas, such as imidazolidinyl urea and diazolidinylurea; phenoxyethanol; sodium methyl paraben, methylparaben,ethylparaben, and propylparaben; potassium sorbate; sodium benzoate;sorbic acid; benzoic acid; formaldehyde; citric acid; sodium citrate;chlorine dioxide; quaternary ammonium compounds, such as benzalkoniumchloride, benzethonium chloride, cetrimide, dequalinium chloride, andcetylpyridinium chloride; mercurial agents, such as phenylmercuricnitrate, phenylmercuric acetate, and thimerosal; piroctone olamine;Vitis vinifera seed oil; and alcoholic agents, for example,chlorobutanol, dichlorobenzyl alcohol, phenylethyl alcohol, and benzylalcohol.

Suitable antioxidants include, but are not limited to, ascorbic acid andits esters, sodium bisulfite, butylated hydroxytoluene, butylatedhydroxyanisole, tocopherols (such as a-tocopherol), tocopheryl acetate,sodium ascorbate/ascorbic acid, ascorbyl palmitate, propyl gallate, andchelating agents like EDTA (e.g., disodium EDTA), citric acid, andsodium citrate.

In certain embodiments, the antioxidant or preservative comprises(3-(4-chlorophenoyx)-2-hydroxypropyl)carbamate.

In certain embodiments, antioxidants or preservatives of the presentinvention may also function as a moisturizer or emollient, for example.

In addition, combinations or mixtures of these preservatives oranti-oxidants may also be used in the formulations of the presentinvention.

6. Active Agents

The active agent may be any material that has a desired effect whenapplied topically to a mammal, particularly a human. Suitable classes ofactive agents include, but are not limited to, antibiotic agents,antimicrobial agents, anti-acne agents, antibacterial agents, antifungalagents, antiviral agents, steroidal anti-inflammatory agents,non-steroidal anti-inflammatory agents, anesthetic agents,antipruriginous agents, antiprotozoal agents, anti-oxidants,antihistamines, vitamins, and hormones. Mixtures of any of these activeagents may also be employed. Additionally, dermatologically-acceptablesalts and esters of any of these agents may be employed.

6.1 Antibiotics

Representative antibiotics include, without limitation, benzoylperoxide, alfa terpineol, octopirox, erythromycin, zinc, tetracyclin,triclosan, azelaic acid and its derivatives, phenoxy ethanol and phenoxypropanol, ethyl acetate, clindamycin (e.g., clindamycin phosphate) andmeclocycline; sebostats such as flavinoids; alpha and beta hydroxyacids; and bile salts such as scymnol sulfate and its derivatives,deoxycholate and cholate. The antibiotic can be an antifungal agent.Suitable antifungal agents include, but are not limited to,clotrimazole, econazole, ketoconazole, itraconazole, miconazole,oxiconazole, sulconazole, butenafine, naftifine, terbinafine,undecylinic acid, tolnaftate, and nystatin. Mixtures of these antibioticagents may also be employed. Additionally, dermatologically-acceptablesalts and esters of any of these agents may be employed.

6.2 Non-Steroidal Anti-Inflammatory Agents

Representative examples of non-steroidal anti-inflammatory agentsinclude, without limitation, oxicams, such as piroxicam, isoxicam,tenoxicam, sudoxicam; salicylates, such as aspirin, disalcid,benorylate, trilisate, safapryn, solprin, diflunisal, and fendosal;acetic acid derivatives, such as diclofenac, fenclofenac, indomethacin,sulindac, tolmetin, isoxepac, furofenac, tiopinac, zidometacin,acematacin, fentiazac, zomepirac, clindanac, oxepinac, felbinac, andketorolac, fenamates, such as mefenamic, meclofenamic, flufenamic,niflumic, and tolfenamic acids; propionic acid derivatives, such asibuprofen, naproxen, benoxaprofen, flurbiprofen, ketoprofen, fenoprofen,fenbufen, indopropfen, pirprofen, carprofen, oxaprozin, pranoprofen,miroprofen, tioxaprofen, suprofen, alminoprofen, and tiaprofenic;pyrazoles, such as phenylbutazone, oxyphenbutazone, feprazone,azapropazone, and trimethazone; and niacinamide. Mixtures of thesenon-steroidal anti-inflammatory agents may also be employed, as well asthe dermatologically acceptable salts and esters of these agents. Forexample, etofenamiate, a flufenamic acid derivative, is particularlyuseful for topical application.

6.3 Steroidal Anti-Inflammatory Agents

Representative examples of steroidal anti-inflammatory drugs include,without limitation, corticosteroids such as hydrocortisone,hydroxyl-triamcinolone, alpha-methyl dexamethasone,dexamethasone-phosphate, beclomethasone dipropionate, clobetasolvalerate, desonide, desoxymethasone, desoxycorticosterone acetate,dexamethasone, dichlorisone, diflorasone diacetate, diflucortolonevalerate, fluadrenolone, fluclorolone acetonide, fludrocortisone,flumethasone pivalate, fluosinolone acetonide, fluocinonide, flucortinebutylesters, fluocortolone, fluprednidene (fluprednylidene) acetate,flurandrenolone, halcinonide, hydrocortisone acetate, hydrocortisonebutyrate, methylprednisolone, triamcinolone acetonide, cortisone,cortodoxone, flucetonide, fludrocortisone, difluorosone diacetate,fluradrenolone, fludrocortisone, difluorosone diacetate, fluradrenoloneacetonide, medrysone, amcinafel, amcinafide, betamethasone and thebalance of its esters (including betamethasone dipropionate),chloroprednisone, chlorprednisone acetate, clocortelone, clescinolone,dichlorisone, diflurprednate, flucloronide, flunisolide,fluoromethalone, fluperolone, fluprednisolone, hydrocortisone valerate,hydrocortisone cyclopentylpropionate, hydrocortamate, meprednisone,paramethasone, prednisolone, prednisone, beclomethasone dipropionate,triamcinolone, and mixtures thereof.

6.4 Anesthetics

Suitable anesthetics include the aminoacylanilide compounds such aslidocaine, prilocalne, bupivacaine, levo-bupivacaine, ropivacaine,mepivacaine and related local anesthetic compounds having varioussubstituents on the ring system or amine nitrogen; the aminoalkylbenzoate compounds, such as procaine, chloroprocaine, propoxycaine,hexylcaine, tetracaine, cyclomethycaine, benoxinate, butacaine,proparacaine, butamben, and related local anesthetic compounds; cocaineand related local anesthetic compounds; amino carbonate compounds suchas diperodon and related local anesthetic compounds; N-phenylamidinecompounds such as phenacaine and related anesthetic compounds;N-aminoalkyl amide compounds such as dibucaine and related localanesthetic compounds; aminoketone compounds such as falicaine, dyclonineand related local anesthetic compounds; and amino ether compounds suchas pramoxine, dimethisoquien, and related local anesthetic compounds;and para-amino benzoic acid esters such as benzocaine. Other suitablelocal anesthetics include ketocaine, dibucaine, amethocaine,propanacaine, and propipocaine.

6.5 Antimicrobial Agents

Suitable antimicrobial agents include, but are not limited to,antibacterial, antifungal, antiprotozoal and antiviral agents, such asbeta-lactam drugs, quinolone drugs, ciprofloxacin, norfloxacin,tetracycline, erythromycin, amikacin, triclosan, doxycycline,capreomycin, chlorhexidine, chlortetracycline, oxytetracycline,clindamycin (e.g., clindamycin phosphate), ethambutol, metronidazole,pentamidine, gentamicin, kanamycin, lineomycin, methacycline,methenamine, minocycline, neomycin, netilmicin, streptomycin,tobramycin, and miconazole. Also included are tetracyclinehydrochloride, framesol, erythromycin estolate, erythromycin stearate(salt), amikacin sulfate, doxycycline hydrochloride, chlorhexidinegluconate, chlorhexidine hydrochloride, chlortetracycline hydrochloride,oxytetracycline hydrochloride, clindamycin hydrochloride, clindamycinphosphate, ethambutol hydrochloride, metronidazole hydrochloride,pentamidine hydrochloride, gentamicin sulfate, kanamycin sulfate,lineomycin hydrochloride, methacycline hydrochloride, methenaminehippurate, methenamine mandelate, minocycline hydrochloride, neomycinsulfate, netilmicin sulfate, paromomycin sulfate, streptomycin sulfate,tobramycin sulfate, miconazole hydrochloride, amanfadine hydrochloride,amanfadine sulfate, triclosan, octopirox, nystatin, tolnaftate,clotrimazole, anidulafungin, micafungin, voriconazole, lanoconazole,ciclopirox and mixtures thereof.

6.6 Keratolytic Agents

Suitable keratolytic agents include, but are not limited to, urea,salicylic acid, papain, sulfur, glycolic acid, pyruvic acid, resorcinol,N-acetylcysteine, retinoids such as retinoic acid (e.g., tretinoin) andits derivatives (e.g., cis and trans isomers, esters), retinol, alphahydroxy acids, beta hydroxy acids, coal tar, and combinations thereof.

7. Purging Gases

In one embodiment, the air in the container charged with the compositionis replaced by an inert gas. In certain embodiments, the inert gas isselected from the group consisting of argon, nitrogen, and mixturesthereof.

8. Buffer Salts

Suitable buffer salts are well-known in the art. Examples of suitablebuffer salts include, but are not limited to sodium citrate, citricacid, sodium phosphate monobasic, sodium phosphate dibasic, sodiumphosphate tribasic, potassium phosphate monobasic, potassium phosphatedibasic, and potassium phosphate tribasic.

9. Viscosity Modifiers

Suitable viscosity adjusting agents (i.e., thickening and thinningagents or viscosity modifying agents) for use in the formulations of thepresent invention include, but are not limited to, protective colloidsor non-ionic gums such as hydroxyethylcellulose, xanthan gum, andsclerotium gum, as well as magnesium aluminum silicate, silica,microcrystalline wax, beeswax, paraffin, and cetyl palmitate. Inaddition, appropriate combinations or mixtures of these viscosityadjusters may be utilized according to the present invention.

10. Additional Constituents

Additional constituents suitable for incorporation into the emulsions ofthe present invention include, but are not limited to: skin protectants,adsorbents, demulcents, emollients, moisturizers, sustained releasematerials, solubilizing agents, skin-penetration agents, skin soothingagents, deodorant agents, antiperspirants, sun screening agents, sunlesstanning agents, vitamins, hair conditioning agents, anti-irritants,anti-aging agents, abrasives, absorbents, anti-caking agents,anti-static agents, astringents (e.g., witch hazel, alcohol, and herbalextracts such as chamomile extract), binders/excipients, bufferingagents, chelating agents, film forming agents, conditioning agents,opacifying agents, lipids, immunomodulators, and pH adjusters (e.g.,citric acid, sodium hydroxide, and sodium phosphate).

For example, lipids normally found in healthy skin (or their functionalequivalents) may be incorporated into the emulsions of the presentinvention. In certain embodiments, the lipid is selected from the groupconsisting of ceramides, cholesterol, and free fatty acids. Examples oflipids include, but are not limited to, ceramide 1, ceramide 2, ceramide3, ceramide 4, ceramide 5, ceramide 6, hydroxypropyl bispalmitamide MEA,and hydroxypropyl bislauramide MEA, and combinations thereof.

Examples of peptides that interact with protein structures of thedermal-epidermal junction include palmitoyl dipeptide-5 diaminobutyloylhydroxythreonine and palmitoyl dipeptide-6 diaminohydroxybutyrate.

Examples of skin soothing agents include, but are not limited to algaeextract, mugwort extract, stearyl glycyrrhetinate, bisabolol, allantoin,aloe, avocado oil, green tea extract, hops extract, chamomile extract,colloidal oatmeal, calamine, cucumber extract, and combinations thereof.

In certain embodiments, the compositions comprise bergamot or bergamotoil. Bergamot oil is a natural skin toner and detoxifier. In certainembodiments, it may prevent premature aging of skin and may haveexcellent effects on oily skin conditions and acne.

Examples of vitamins include, but are not limited to, vitamins A, D, E,K, and combinations thereof. Vitamin analogues are also contemplated;for example the vitamin D analogues calcipotriene or calcipotriol.

In certain embodiments, the vitamin may be present as tetrahexyldecylascorbate. This compound exhibits anti-oxidant activity, inhibitinglipid peroxidation. In certain embodiments, use can mitigate thedamaging effects of UV exposure. Studies have shown it to stimulatecollagen production as well as clarifying and brightening the skin byinhibiting melanogenesis (the production of pigment) thereby promoting amore even skin tone.

Examples of sunscreens include, but are not limited to, p-aminobenzoicacid, avobenzone, cinoxate, dioxybenzone, homosalate, menthylanthranilate, octocrylene, octyl methoxycinnamate, octyl salicylate,oxybenzone, padimate O, phenylbenzimidazole sulfonic acid,sulisobenzone, titanium dioxide, trolamine salicylate, zinc oxide,4-methylbenzylidene camphor, methylene bis-benzotriazolyltetramethylbutylphenol, bis-ethylhexyloxyphenol methoxyphenyl triazine,terephthalylidene dicamphor sulfonic acid, drometrizole trisiloxane,disodium phenyl dibenzimidazole tetrasulfonate, diethylaminohydroxybenzoyl hexyl benzoate, octyl triazone, diethylhexyl butamidotriazone, polysilicone-15, and combinations thereof.

Suitable fragrances and colors may be used in the formulations of thepresent invention. Examples of fragrances and colors suitable for use intopical products are known in the art.

Suitable immunomodulators include, but are not limited to,tetrachlorodecaoxide, deoxycholic acid, tacrolimus, pimecrolimus, andbeta-glucan.

In certain embodiments, palmitoyl-lysyl-valyl-lysine bistrifluoroacetateis added. This peptide stimulates collagen synthesis in humanfibroblasts.

Often, one constituent of a composition may accomplish severalfunctions. In one embodiment, the present invention relates toconstituents that may act as a lubricant, an emollient, or askin-penetrating agent. In one embodiment, the multi-functionalconstituent is socetyl stearate, isopropyl isostearate, isopropylpalmitate, or isopropyl myristate.

Exemplary Microemulsions of the Invention

In certain embodiments, the invention relates to a microemulsion,comprising: an aqueous phase; a first surfactant; and a secondsurfactant.

In certain embodiments, the invention relates to a microemulsion,consisting essentially of: an aqueous phase; a first surfactant; and asecond surfactant.

In certain embodiments, the invention relates to a microemulsion,consisting of: an aqueous phase; a first surfactant; and a secondsurfactant.

In certain embodiments, the invention relates to any one of theaforementioned microemulsions, wherein the aqueous phase is present inan amount from about 75% to about 95% by weight of the microemulsion. Incertain embodiments, the invention relates to any one of theaforementioned microemulsions, wherein the aqueous phase is present inabout 75%, about 80%, about 85%, about 90%, or about 95% by weight ofthe microemulsion. In certain embodiments, the invention relates to anyone of the aforementioned microemulsions, wherein the aqueous phase ispresent in about 80% by weight of the microemulsion. In certainembodiments, the invention relates to any one of the aforementionedmicroemulsions, wherein the aqueous phase is present in about 90% byweight of the microemulsion.

In certain embodiments, the invention relates to any one of theaforementioned microemulsions, wherein the aqueous phase is water.

In certain embodiments, the invention relates to any one of theaforementioned microemulsions, wherein the aqueous phase compriseswater.

In certain embodiments, the invention relates to any one of theaforementioned microemulsions, wherein the aqueous phase comprises amoisturizer or emollient.

In certain embodiments, the moisturizer or emollient is selected fromthe group consisting of panthenol, petrolatum, lactic acid, glycerol,butylene glycol, sodium PCA, sodium hyaluronate, Carbowax 200, Carbowax400, Carbowax 800, cetyl palmitate, PPG-15 stearyl ether, lanolinalcohol, lanolin, lanolin derivatives, cholesterol, isostearylneopentanoate, octyl stearate, mineral oil, isocetyl stearate, myristylmyristate, octyl dodecanol, 2-ethylhexyl palmitate, dimethicone,dimethicone/divinyldimethicone/silsesquioxance cross polymer,polydimethylsiloxane, caprylic/capric triglyceride, shea butter, jojobawax, sunflower wax, mimosa wax, phenyl trimethicone, cyclomethicone,C₁₂-C₁₅ alkyl benzoates, C₁₂-C₁₅ alkyl ethylhexanoates, dimethiconol,propylene glycol, Theobroma grandiflorum seed butter, ceramide 2,hydroxypropyl bispalmitamide MEA, hydroxypropyl bislauramide MEA,hydroxypropyl bisisostearamide MEA,1,3-bis(N-2-(hydroxyethyl)stearoylamino)-2-hydroxy propane,bis-hydroxyethyl tocopherylsuccinoylamido hydroxypropane, urea, aloe,allantoin, glycyrrhetinic acid, safflower oil, oleyl alcohol, stearicacid, dicaprylate/dicaprate, diethyl sebacate, isostearyl alcohol,pentylene glycol,1,3-bis(N-2-(hydroxyethyl)palmitoylamino)-2-hydroxypropane, hydrolyzedrice extract, cetyl alcohol, dipalmitoyl hydroxyproline, andcombinations/mixtures thereof.

In certain embodiments, the moisturizer or emollient is selected fromthe group consisting of panthenol, allantoin, sodium hyaluraonate,pentylene glycol, and combinations/mixtures thereof.

In certain embodiments, the moisturizer or emollient is present in anamount from about 0.8% to about 2.3% by weight of the aqueous phase. Incertain embodiments, the moisturizer or emollient is present in about0.8%, about 0.9%, about 1.0%, about 1.1%, about 1.2%, about 1.3%, about1.4%, about 1.5%, about 1.6%, about 1.7%, about 1.8%, about 1.9%, about2.0%, about 2.1%, about 2.2% or about 2.3% by weight of the aqueousphase.

In certain embodiments, the moisturizer or emollient comprisespanthenol; and the panthenol is present in an amount from about 0.5% toabout 1.5% by weight of the aqueous phase. In certain embodiments, thepanthenol is present in about 0.5%, about 0.6%, about 0.7%, about 0.8%,about 0.9%, about 1.0%, about 1.1%, about 1.2%, about 1.3%, about 1.4%,or about 1.5% by weight of the aqueous phase. In certain embodiments,the panthenol is present in about 1.0% by weight of the aqueous phase.

In certain embodiments, the moisturizer or emollient comprisesallantoin; and the allantoin is present in an amount from about 0.2% toabout 0.6% by weight of the aqueous phase. In certain embodiments, theallantoin is present in about 0.2%, about 0.3%, about 0.4%, about 0.5%,or about 0.6% by weight of the aqueous phase. In certain embodiments,the allantoin is present in about 0.4% by weight of the aqueous phase.

In certain embodiments, the moisturizer or emollient comprises sodiumhyaluronate; and the sodium hyaluronate is present in an amount fromabout 0.005% to about 0.02% by weight of the aqueous phase. In certainembodiments, the sodium hyaluronate is present in about 0.005%, about0.01%, about 0.015%, or about 0.02% by weight of the aqueous phase. Incertain embodiments, the sodium hyaluronate is present in about 0.01% byweight of the aqueous phase.

In certain embodiments, the moisturizer or emollient comprises pentyleneglycol; and the pentylene glycol is present in an amount from about 0.1%to about 0.3% by weight of the aqueous phase. In certain embodiments,the pentylene glycol is present in about 0.1%, about 0.2%, or about 0.3%by weight of the aqueous phase. In certain embodiments, the pentyleneglycol is present in about 0.2% by weight of the aqueous phase.

In certain embodiments, the invention relates to any one of theaforementioned microemulsions, wherein the aqueous phase comprises ananti-inflammatory agent. In certain embodiments, the anti-inflammatoryagent is niacinamide.

In certain embodiments, the anti-inflammatory agent is present in anamount from about 0.5% to about 2% by weight of the aqueous phase. Incertain embodiments, the anti-inflammatory agent is present in about0.5%, about 1%, about 1.5%, or about 2% by weight of the aqueous phase.In certain embodiments, the anti-inflammatory agent is present in about1% by weight of the aqueous phase.

In certain embodiments, the invention relates to any one of theaforementioned microemulsions, wherein the aqueous phase comprises anantioxidant or preservative.

In certain embodiments, the antioxidant or preservative is selected fromthe group consisting of imidazolidinyl urea, diazolidinyl urea,phenoxyethanol, sodium methyl paraben, methylparaben, ethylparaben,propylparaben, potassium sorbate, sodium benzoate, sorbic acid, benzoicacid, formaldehyde, citric acid, sodium citrate, chlorine dioxide,benzalkonium chloride, benzethonium chloride, cetrimide, dequaliniumchloride, cetylpyridinium chloride, phenylmercuric nitrate,phenylmercuric acetate, thimerosal, piroctone olamine, Vitis viniferaseed oil, chlorobutanol, dichlorobenzyl alcohol, phenylethyl alcohol,benzyl alcohol, ascorbic acid, sodium bisulfite, butylatedhydroxytoluene, butylated hydroxyanisole, α-tocopherol, tocopherylacetate, sodium ascorbate/ascorbic acid, ascorbyl palmitate, propylgallate, disodium EDTA, citric acid, and sodium citrate, andcombinations/mixtures thereof.

In certain embodiments, the antioxidant or preservative is selected fromthe group consisting of potassium sorbate, sodium benzoate, disodiumEDTA, and combinations/mixtures thereof.

In certain embodiments, the antioxidant or preservative is present in anamount from about 0.2% to about 0.6% by weight of the aqueous phase.

In certain embodiments, the antioxidant or preservative comprisespotassium sorbate; and the potassium sorbate is present in an amountfrom about 0.07% to about 0.23% by weight of the aqueous phase. Incertain embodiments, the potassium sorbate is present in about 0.07%,about 0.08%, about 0.09%, about 0.1%, about 0.11%, about 0.12%, about0.13%, about 0.14%, about 0.15%, about 0.16%, about 0.17%, about 0.18%,about 0.19%, about 0.2%, about 0.21%, about 0.22% or about 0.23% byweight of the aqueous phase. In certain embodiments, the potassiumsorbate is present in about 0.15% by weight of the aqueous phase.

In certain embodiments, the antioxidant or preservative comprises sodiumbenzoate; and the sodium benzoate is present in an amount from about0.07% to about 0.23% by weight of the aqueous phase. In certainembodiments, the sodium benzoate is present in about 0.07%, about 0.08%,about 0.09%, about 0.1%, about 0.11%, about 0.12%, about 0.13%, about0.14%, about 0.15%, about 0.16%, about 0.17%, about 0.18%, about 0.19%,about 0.2%, about 0.21%, about 0.22% or about 0.23% by weight of theaqueous phase. In certain embodiments, the sodium benzoate is present inabout 0.15% by weight of the aqueous phase.

In certain embodiments, the antioxidant or preservative comprisesdisodium EDTA; and the disodium EDTA is present in an amount from about0.05% to about 0.15% by weight of the aqueous phase. In certainembodiments, the disodium EDTA is present in about 0.05%, about 0.06%,about 0.07%, about 0.08%, about 0.09%, about 0.10%, about 0.11%, about0.12%, about 0.13%, about 0.14%, or about 0.15% by weight of the aqueousphase. In certain embodiments, the disodium EDTA is present in about0.10% by weight of the aqueous phase.

In certain embodiments, the invention relates to any one of theaforementioned microemulsions, wherein the aqueous phase comprises a pHadjuster. In certain embodiments, the pH adjuster is sodium hydroxide.

In certain embodiments, the pH adjuster is present in an amount fromabout 0.02% to about 0.1% by weight of the aqueous phase. In certainembodiments, the pH adjuster is present in about 0.02%, about 0.04%,about 0.06%, about 0.08%, or about 0.1% by weight of the aqueous phase.

In certain embodiments, the invention relates to any one of theaforementioned microemulsions, wherein the first surfactant is presentin an amount from about 1% to about 8% by weight of the microemulsion.In certain embodiments, the invention relates to any one of theaforementioned microemulsions, wherein the first surfactant is presentin about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%,or about 8% by weight of the microemulsion. In certain embodiments, theinvention relates to any one of the aforementioned microemulsions,wherein the first surfactant is present in about 3% by weight of themicroemulsion. In certain embodiments, the invention relates to any oneof the aforementioned microemulsions, wherein the first surfactant ispresent in about 5% by weight of the microemulsion.

In certain embodiments, the invention relates to any one of theaforementioned microemulsions, wherein the first surfactant comprises acyclodextrin or a derivative of a cyclodextrin. In certain embodiments,the invention relates to any one of the aforementioned microemulsions,wherein the first surfactant is a cyclodextrin or a derivative of acyclodextrin. In certain embodiments, the invention relates to any oneof the aforementioned microemulsions, wherein the first surfactant is acyclodextrin. In certain embodiments, the invention relates to any oneof the aforementioned microemulsions, wherein the first surfactant ishydroxypropyl α-cyclodextrin, hydroxypropyl β-cyclodextrin, orhydroxypropyl γ-cyclodextrin. In certain embodiments, the inventionrelates to any one of the aforementioned microemulsions, wherein thefirst surfactant is hydroxypropyl β-cyclodextrin.

In certain embodiments, the invention relates to any one of theaforementioned microemulsions, wherein the second surfactant is presentin an amount from about 4% to about 22% by weight of the microemulsion.In certain embodiments, the invention relates to any one of theaforementioned microemulsions, wherein the second surfactant is presentin about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%,about 17%, about 18%, about 19%, about 20%, about 21%, or about 22% byweight of the microemulsion. In certain embodiments, the inventionrelates to any one of the aforementioned microemulsions, wherein thesecond surfactant is present in about 7% by weight of the microemulsion.In certain embodiments, the invention relates to any one of theaforementioned microemulsions, wherein the second surfactant is presentin about 15% by weight of the microemulsion.

In certain embodiments, the invention relates to any one of theaforementioned microemulsions, wherein the second surfactant comprisescaprylocaproyl macrogol-8 glycerides or caprylocaproyl polyoxyl-8glycerides. In certain embodiments, the invention relates to any one ofthe aforementioned microemulsions, wherein the second surfactant iscaprylocaproyl macrogol-8 glycerides or caprylocaproyl polyoxyl-8glycerides, or a combination thereof.

In certain embodiments, the invention relates to a microemulsion,comprising:

-   -   water, in an amount of about 80% by weight of the microemulsion;    -   hydroxypropyl β-cyclodextrin, in an amount of about 5% by weight        of the microemulsion; and    -   caprylocaproyl macrogol-8 glycerides or caprylocaproyl        polyoxyl-8 glycerides, in an amount of about 15% by weight of        the microemulsion.

In certain embodiments, the invention relates to a microemulsion,consisting essentially of:

-   -   water, in an amount of about 80% by weight of the microemulsion;    -   hydroxypropyl β-cyclodextrin, in an amount of about 5% by weight        of the microemulsion; and    -   caprylocaproyl macrogol-8 glycerides or caprylocaproyl        polyoxyl-8 glycerides, in an amount of about 15% by weight of        the microemulsion.

In certain embodiments, the invention relates to a microemulsion,consisting of:

-   -   water, in an amount of about 80% by weight of the microemulsion;    -   hydroxypropyl β-cyclodextrin, in an amount of about 5% by weight        of the microemulsion; and    -   caprylocaproyl macrogol-8 glycerides or caprylocaproyl        polyoxyl-8 glycerides, in an amount of about 15% by weight of        the microemulsion.

In certain embodiments, the invention relates to a microemulsion,comprising:

-   -   water, in an amount of about 90% by weight of the microemulsion;    -   hydroxypropyl β-cyclodextrin, in an amount of about 3% by weight        of the microemulsion; and    -   caprylocaproyl macrogol-8 glycerides or caprylocaproyl        polyoxyl-8 glycerides, in an amount of about 7% by weight of the        microemulsion.

In certain embodiments, the invention relates to a microemulsion,consisting essentially of:

-   -   water, in an amount of about 90% by weight of the microemulsion;    -   hydroxypropyl β-cyclodextrin, in an amount of about 3% by weight        of the microemulsion; and    -   caprylocaproyl macrogol-8 glycerides or caprylocaproyl        polyoxyl-8 glycerides, in an amount of about 7% by weight of the        microemulsion.

In certain embodiments, the invention relates to a microemulsion,consisting of:

-   -   water, in an amount of about 90% by weight of the microemulsion;    -   hydroxypropyl β-cyclodextrin, in an amount of about 3% by weight        of the microemulsion; and    -   caprylocaproyl macrogol-8 glycerides or caprylocaproyl        polyoxyl-8 glycerides, in an amount of about 7% by weight of the        microemulsion.

In certain embodiments, the invention relates to any one of theaforementioned microemulsions, wherein the microemulsion does notcomprise methanol, ethanol, propanol, or butanol.

Exemplary Properties of Microemulsions of the Invention

In certain embodiments, the invention relates to any one of theaforementioned microemulsions, wherein the microemulsion issubstantially optically clear.

In certain embodiments, the invention relates to any one of theaforementioned microemulsions, wherein the microemulsion issubstantially stable at room temperature.

Exemplary Methods of Making Microemulsions

In certain embodiments, the invention relates to a method of making anyone of the aforementioned microemulsions, comprising the step ofcombining the aqueous phase, the first surfactant, and the secondsurfactant.

Exemplary Micro Emulsions Comprising Active Agents

In certain embodiments, the invention relates to an activeagent-containing microemulsion, comprising: an aqueous phase; an activeagent; a first surfactant; and a second surfactant.

In certain embodiments, the invention relates to an activeagent-containing microemulsion, consisting essentially of: an aqueousphase; an active agent; a first surfactant; and a second surfactant.

In certain embodiments, the invention relates to an activeagent-containing microemulsion, consisting of: an aqueous phase; anactive agent; a first surfactant; and a second surfactant.

In certain embodiments, the invention relates to any one of theaforementioned active agent-containing microemulsions, wherein theactive agent comprises retinol. In certain embodiments, the inventionrelates to any one of the aforementioned active agent-containingmicroemulsions, wherein the active agent is retinol.

In certain embodiments, the invention relates to any one of theaforementioned active agent-containing microemulsions, wherein theactive agent-containing microemulsion comprises any one of theaforementioned microemulsions; and an active agent.

In certain embodiments, the invention relates to any one of theaforementioned active agent-containing microemulsions, wherein theactive agent is present in an amount from about 0.01% to about 5% byweight of the active agent-containing microemulsion. In certainembodiments, the invention relates to any one of the aforementionedactive agent-containing microemulsions, wherein the active agent ispresent in about 0.01%, about 0.02%, about 0.04%, about 0.06%, about0.08%, about 0.1%, about 0.2%, about 0.3%, about 0.4%, about 0.5%, about0.6%, about 0.7%, about 0.8%, about 0.9%, about 1.0%, about 1.2%, about1.4%, about 1.6%, about 1.8%, about 2.0%, about 2.2%, about 2.4%, about2.6%, about 2.8%, about 3.0%, about 3.5%, about 4.0%, about 4.5%, orabout 5.0% by weight of the active agent-containing microemulsion. Incertain embodiments, the invention relates to any one of theaforementioned active agent-containing microemulsions, wherein theactive agent is present in about 0.06% by weight of the activeagent-containing microemulsion. In certain embodiments, the inventionrelates to any one of the aforementioned active agent-containingmicroemulsions, wherein the active agent is present in about 1.2% byweight of the active agent-containing microemulsion.

Exemplary Properties of Active Agent-Containing Microemulsions of theInvention

In certain embodiments, the invention relates to any one of theaforementioned active agent-containing microemulsions, wherein theactive agent-containing microemulsion is substantially optically clear.

In certain embodiments, the invention relates to any one of theaforementioned active agent-containing microemulsions, wherein theactive agent-containing microemulsion is substantially stable at roomtemperature.

Exemplary Methods of Making Microemulsions

In certain embodiments, the invention relates to a method of making anyone of the aforementioned active agent-containing microemulsions,comprising the step of combining the aqueous phase, the firstsurfactant, the second surfactant, and the active agent.

Exemplary Formulations of the Invention

In certain embodiments, the invention relates to a formulationcomprising

-   -   any one of the aforementioned microemulsions; an active agent; a        moisturizer or emollient; a third surfactant; an antioxidant or        preservative; a viscosity modifying agent; and a pH adjuster.

In certain embodiments, the invention relates to a formulation,comprising:

-   -   any one of the aforementioned microemulsions, in an amount from        about 28% to about 84% by weight of the formulation;    -   retinol, from about 0.08% to about 2.5% by weight of the        formulation;    -   isononyl isononanoate, from about 2% to about 9% by weight of        the formulation;    -   cetyl alcohol, glyceryl stearate, PEG-75 stearate, ceteth-20,        and steareth-20, taken together, from about 2.5% to about 7.5%        by weight of the formulation;    -   pentylene glycol, from about 0.1% to about 0.4% by weight of the        formulation;    -   C₁₂-C₁₅ alkyl ethylhexanoates, from about 1% to about 6% by        weight of the formulation;    -   Palmitoyl-lysyl-valyl-lysine bistrifluoroacetate and glycerin,        taken together, from about 1% to about 5% by weight of the        formulation;    -   Jojoba wax, sunflower wax, and mimosa wax, taken together, from        about 1% to about 3% by weight of the formulation;    -   Shea butter, from about 1% to about 3% by weight of the        formulation;    -   Caprylic/capric triglyceride, from about 1% to about 3% by        weight of the formulation;    -   Polydimethylsiloxane, from about 1% to about 3% by weight of the        formulation;    -   Dimethicone/divinyldimethicone/silsesquioxane cross polymer,        from about 1% to about 3% by weight of the formulation;    -   Dipalmitoyl hydroxyproline, from about 0.5% to about 1.5% by        weight of the formulation;    -   Cetyl alcohol, from about 0.5% to about 2.2% by weight of the        formulation;    -   Sodium hyaluronate, from about 0.005% to about 0.02% by weight        of the formulation;    -   Panthenol, from about 0.5% to about 1.5% by weight of the        formulation;    -   Niacinamide, from about 0.5% to about 1.5% by weight of the        formulation;    -   Butylene glycol and hydrolyzed rice extract, taken together,        from about 0.5% to about 1.5% by weight of the formulation;    -   Algae extract and mugwort extract, taken together, from about        0.5% to about 1.5% by weight of the formulation;    -   Glycerin, palmitoyl dipeptide-5 diaminobutyloyl        hydroxythreonine, and palmitoyl dipeptide-6        diaminohydroxybutyrate, taken together, from about 0.5% to about        1.5% by weight of the formulation;    -   Magnesium aluminum silicate, from about 0.3% to about 2.2% by        weight of the formulation;    -   Tocopheryl acetate, from about 0.25% to about 0.75% by weight of        the formulation;    -   Tetrahexyldecyl ascorbate, from about 0.25% to about 0.75% by        weight of the formulation;    -   Allantoin, from about 0.2% to about 0.6% by weight of the        formulation;    -   Bergamot, from about 0.15% to about 0.45% by weight of the        formulation;    -   (3-(4-chlorophenoxy)-2-hydroxypropyl)carbamate, from about 0.15%        to about 0.45% by weight of the formulation;    -   Sodium ascorbate, from about 0.1% to about 0.4% by weight of the        formulation;    -   Bisabolol, from about 0.1% to about 0.3% by weight of the        formulation;    -   Tocopherol, from about 0.05% to about 0.25% by weight of the        formulation;    -   Potassium sorbate, from about 0.05% to about 0.25% by weight of        the formulation;    -   Sodium benzoate, from about 0.05% to about 0.25% by weight of        the formulation;    -   Butylated hydroxytoluene, from about 0.05% to about 0.15% by        weight of the formulation;    -   Stearyl glycyrrhetinate, from about 0.05% to about 0.15% by        weight of the formulation;    -   Xanthan gum, from about 0.05% to about 0.3% by weight of the        formulation;    -   Disodium EDTA, from about 0.05% to about 0.15% by weight of the        formulation; and    -   Sodium hydroxide, from about 0.02% to about 0.06% by weight of        the formulation,    -   wherein the sum of the amounts of the components is less than or        equal to 100%.

In certain embodiments, the invention relates to a formulation,consisting essentially of:

-   -   any one of the aforementioned microemulsions, in an amount from        about 28% to about 84% by weight of the formulation;    -   retinol, from about 0.08% to about 2.5% by weight of the        formulation;    -   isononyl isononanoate, from about 2% to about 9% by weight of        the formulation;    -   cetyl alcohol, glyceryl stearate, PEG-75 stearate, ceteth-20,        and steareth-20, taken together, from about 2.5% to about 7.5%        by weight of the formulation;    -   pentylene glycol, from about 0.1% to about 0.4% by weight of the        formulation;    -   C₁₂-C₁₅ alkyl ethylhexanoates, from about 1% to about 6% by        weight of the formulation;    -   Palmitoyl-lysyl-valyl-lysine bistrifluoroacetate and glycerin,        taken together, from about 1% to about 5% by weight of the        formulation;    -   Jojoba wax, sunflower wax, and mimosa wax, taken together, from        about 1% to about 3% by weight of the formulation;    -   Shea butter, from about 1% to about 3% by weight of the        formulation;    -   Caprylic/capric triglyceride, from about 1% to about 3% by        weight of the formulation;    -   Polydimethylsiloxane, from about 1% to about 3% by weight of the        formulation;    -   Dimethicone/divinyldimethicone/silsesquioxane cross polymer,        from about 1% to about 3% by weight of the formulation;    -   Dipalmitoyl hydroxyproline, from about 0.5% to about 1.5% by        weight of the formulation;    -   Cetyl alcohol, from about 0.5% to about 2.2% by weight of the        formulation;    -   Sodium hyaluronate, from about 0.005% to about 0.02% by weight        of the formulation;    -   Panthenol, from about 0.5% to about 1.5% by weight of the        formulation;    -   Niacinamide, from about 0.5% to about 1.5% by weight of the        formulation;    -   Butylene glycol and hydrolyzed rice extract, taken together,        from about 0.5% to about 1.5% by weight of the formulation;    -   Algae extract and mugwort extract, taken together, from about        0.5% to about 1.5% by weight of the formulation;    -   Glycerin, palmitoyl dipeptide-5 diaminobutyloyl        hydroxythreonine, and palmitoyl dipeptide-6        diaminohydroxybutyrate, taken together, from about 0.5% to about        1.5% by weight of the formulation;    -   Magnesium aluminum silicate, from about 0.3% to about 2.2% by        weight of the formulation;    -   Tocopheryl acetate, from about 0.25% to about 0.75% by weight of        the formulation;    -   Tetrahexyldecyl ascorbate, from about 0.25% to about 0.75% by        weight of the formulation;    -   Allantoin, from about 0.2% to about 0.6% by weight of the        formulation;    -   Bergamot, from about 0.15% to about 0.45% by weight of the        formulation;    -   (3-(4-chlorophenoxy)-2-hydroxypropyl)carbamate, from about 0.15%        to about 0.45% by weight of the formulation;    -   Sodium ascorbate, from about 0.1% to about 0.4% by weight of the        formulation;    -   Bisabolol, from about 0.1% to about 0.3% by weight of the        formulation;    -   Tocopherol, from about 0.05% to about 0.25% by weight of the        formulation;    -   Potassium sorbate, from about 0.05% to about 0.25% by weight of        the formulation;    -   Sodium benzoate, from about 0.05% to about 0.25% by weight of        the formulation;    -   Butylated hydroxytoluene, from about 0.05% to about 0.15% by        weight of the formulation;    -   Stearyl glycyrrhetinate, from about 0.05% to about 0.15% by        weight of the formulation;    -   Xanthan gum, from about 0.05% to about 0.3% by weight of the        formulation;    -   Disodium EDTA, from about 0.05% to about 0.15% by weight of the        formulation; and    -   Sodium hydroxide, from about 0.02% to about 0.06% by weight of        the formulation,    -   wherein the sum of the amounts of the components is less than or        equal to 100%.

In certain embodiments, the invention relates to a formulation,consisting of:

-   -   any one of the aforementioned microemulsions, in an amount from        about 28% to about 84% by weight of the formulation;    -   retinol, from about 0.08% to about 2.5% by weight of the        formulation;    -   isononyl isononanoate, from about 2% to about 9% by weight of        the formulation;    -   cetyl alcohol, glyceryl stearate, PEG-75 stearate, ceteth-20,        and steareth-20, taken together, from about 2.5% to about 7.5%        by weight of the formulation;    -   pentylene glycol, from about 0.1% to about 0.4% by weight of the        formulation;    -   C₁₂-C₁₅ alkyl ethylhexanoates, from about 1% to about 6% by        weight of the formulation;    -   Palmitoyl-lysyl-valyl-lysine bistrifluoroacetate and glycerin,        taken together, from about 1% to about 5% by weight of the        formulation;    -   Jojoba wax, sunflower wax, and mimosa wax, taken together, from        about 1% to about 3% by weight of the formulation;    -   Shea butter, from about 1% to about 3% by weight of the        formulation;    -   Caprylic/capric triglyceride, from about 1% to about 3% by        weight of the formulation;    -   Polydimethylsiloxane, from about 1% to about 3% by weight of the        formulation;    -   Dimethicone/divinyldimethicone/silsesquioxane cross polymer,        from about 1% to about 3% by weight of the formulation;    -   Dipalmitoyl hydroxyproline, from about 0.5% to about 1.5% by        weight of the formulation;    -   Cetyl alcohol, from about 0.5% to about 2.2% by weight of the        formulation;    -   Sodium hyaluronate, from about 0.005% to about 0.02% by weight        of the formulation;    -   Panthenol, from about 0.5% to about 1.5% by weight of the        formulation;    -   Niacinamide, from about 0.5% to about 1.5% by weight of the        formulation;    -   Butylene glycol and hydrolyzed rice extract, taken together,        from about 0.5% to about 1.5% by weight of the formulation;    -   Algae extract and mugwort extract, taken together, from about        0.5% to about 1.5% by weight of the formulation;    -   Glycerin, palmitoyl dipeptide-5 diaminobutyloyl        hydroxythreonine, and palmitoyl dipeptide-6        diaminohydroxybutyrate, taken together, from about 0.5% to about        1.5% by weight of the formulation;    -   Magnesium aluminum silicate, from about 0.3% to about 2.2% by        weight of the formulation;    -   Tocopheryl acetate, from about 0.25% to about 0.75% by weight of        the formulation;    -   Tetrahexyldecyl ascorbate, from about 0.25% to about 0.75% by        weight of the formulation;    -   Allantoin, from about 0.2% to about 0.6% by weight of the        formulation;    -   Bergamot, from about 0.15% to about 0.45% by weight of the        formulation;    -   (3-(4-chlorophenoxy)-2-hydroxypropyl)carbamate, from about 0.15%        to about 0.45% by weight of the formulation;    -   Sodium ascorbate, from about 0.1% to about 0.4% by weight of the        formulation;    -   Bisabolol, from about 0.1% to about 0.3% by weight of the        formulation;    -   Tocopherol, from about 0.05% to about 0.25% by weight of the        formulation;    -   Potassium sorbate, from about 0.05% to about 0.25% by weight of        the formulation;    -   Sodium benzoate, from about 0.05% to about 0.25% by weight of        the formulation;    -   Butylated hydroxytoluene, from about 0.05% to about 0.15% by        weight of the formulation;    -   Stearyl glycyrrhetinate, from about 0.05% to about 0.15% by        weight of the formulation;    -   Xanthan gum, from about 0.05% to about 0.3% by weight of the        formulation;    -   Disodium EDTA, from about 0.05% to about 0.15% by weight of the        formulation; and    -   Sodium hydroxide, from about 0.02% to about 0.06% by weight of        the formulation,    -   wherein the sum of the amounts of the components is equal to        100%.

In certain embodiments, the invention relates to a formulation,comprising:

-   -   any one of the aforementioned microemulsions, in about 55.19% by        weight of the formulation;    -   retinol, in about 1.33% by weight of the formulation;    -   isononyl isononanoate, in about 6.00% by weight of the        formulation;    -   cetyl alcohol, glyceryl stearate, PEG-75 stearate, ceteth-20,        and steareth-20, taken together, in about 5.00% by weight of the        formulation;    -   pentylene glycol, in about 0.25% by weight of the formulation;    -   C₁₂-C₁₅ alkyl ethylhexanoates, in about 4.00% by weight of the        formulation;    -   Palmitoyl-lysyl-valyl-lysine bistrifluoroacetate and glycerin,        taken together, in about 2.50% by weight of the formulation;    -   Jojoba wax, sunflower wax, and mimosa wax, taken together, in        about 2.00% by weight of the formulation;    -   Shea butter, in about 2.00% by weight of the formulation;    -   Caprylic/capric triglyceride, in about 2.00% by weight of the        formulation;    -   Polydimethylsiloxane, in about 1.50% by weight of the        formulation;    -   Dimethicone/divinyldimethicone/silsesquioxane cross polymer, in        about 1.50% by weight of the formulation;    -   Dipalmitoyl hydroxyproline, in about 1.00% by weight of the        formulation;    -   Cetyl alcohol, in about 1.00% by weight of the formulation;    -   Sodium hyaluronate, in about 0.01% by weight of the formulation;    -   Panthenol, in about 1.00% by weight of the formulation;    -   Niacinamide, in about 1.00% by weight of the formulation;    -   Butylene glycol and hydrolyzed rice extract, taken together, in        about 1.00% by weight of the formulation;    -   Algae extract and mugwort extract, taken together, in about        1.00% by weight of the formulation;    -   Glycerin, palmitoyl dipeptide-5 diaminobutyloyl        hydroxythreonine, and palmitoyl dipeptide-6        diaminohydroxybutyrate, taken together, in about 1.00% by weight        of the formulation;    -   Magnesium aluminum silicate, in about 0.60% by weight of the        formulation;    -   Tocopheryl acetate, in about 0.50% by weight of the formulation;    -   Tetrahexyldecyl ascorbate, in about 0.50% by weight of the        formulation;    -   Allantoin, in about 0.40% by weight of the formulation;    -   Bergamot, in about 0.30% by weight of the formulation;    -   (3-(4-chlorophenoxy)-2-hydroxypropyl)carbamate, in about 0.30%        by weight of the formulation;    -   Sodium ascorbate, in about 0.24% by weight of the formulation;    -   Bisabolol, in about 0.20% by weight of the formulation;    -   Tocopherol, in about 0.16% by weight of the formulation;    -   Potassium sorbate, in about 0.15% by weight of the formulation;    -   Sodium benzoate, in about 0.15% by weight of the formulation;    -   Butylated hydroxytoluene, in about 0.10% by weight of the        formulation;    -   Stearyl glycyrrhetinate, in about 0.10% by weight of the        formulation;    -   Xanthan gum, in about 0.10% by weight of the formulation;    -   Disodium EDTA, in about 0.10% by weight of the formulation; and    -   Sodium hydroxide, in about 0.04% by weight of the formulation.

In certain embodiments, the invention relates to a formulation,consisting essentially of:

-   -   any one of the aforementioned microemulsions, in about 55.19% by        weight of the formulation;    -   retinol, in about 1.33% by weight of the formulation;    -   isononyl isononanoate, in about 6.00% by weight of the        formulation;    -   cetyl alcohol, glyceryl stearate, PEG-75 stearate, ceteth-20,        and steareth-20, taken together, in about 5.00% by weight of the        formulation;    -   pentylene glycol, in about 0.25% by weight of the formulation;    -   C₁₂-C₁₅ alkyl ethylhexanoates, in about 4.00% by weight of the        formulation;    -   Palmitoyl-lysyl-valyl-lysine bistrifluoroacetate and glycerin,        taken together, in about 2.50% by weight of the formulation;    -   Jojoba wax, sunflower wax, and mimosa wax, taken together, in        about 2.00% by weight of the formulation;    -   Shea butter, in about 2.00% by weight of the formulation;    -   Caprylic/capric triglyceride, in about 2.00% by weight of the        formulation;    -   Polydimethylsiloxane, in about 1.50% by weight of the        formulation;    -   Dimethicone/divinyldimethicone/silsesquioxane cross polymer, in        about 1.50% by weight of the formulation;    -   Dipalmitoyl hydroxyproline, in about 1.00% by weight of the        formulation;    -   Cetyl alcohol, in about 1.00% by weight of the formulation;    -   Sodium hyaluronate, in about 0.01% by weight of the formulation;    -   Panthenol, in about 1.00% by weight of the formulation;    -   Niacinamide, in about 1.00% by weight of the formulation;    -   Butylene glycol and hydrolyzed rice extract, taken together, in        about 1.00% by weight of the formulation;    -   Algae extract and mugwort extract, taken together, in about        1.00% by weight of the formulation;    -   Glycerin, palmitoyl dipeptide-5 diaminobutyloyl        hydroxythreonine, and palmitoyl dipeptide-6        diaminohydroxybutyrate, taken together, in about 1.00% by weight        of the formulation;    -   Magnesium aluminum silicate, in about 0.60% by weight of the        formulation;    -   Tocopheryl acetate, in about 0.50% by weight of the formulation;    -   Tetrahexyldecyl ascorbate, in about 0.50% by weight of the        formulation;    -   Allantoin, in about 0.40% by weight of the formulation;    -   Bergamot, in about 0.30% by weight of the formulation;    -   (3-(4-chlorophenoxy)-2-hydroxypropyl)carbamate, in about 0.30%        by weight of the formulation;    -   Sodium ascorbate, in about 0.24% by weight of the formulation;    -   Bisabolol, in about 0.20% by weight of the formulation;    -   Tocopherol, in about 0.16% by weight of the formulation;    -   Potassium sorbate, in about 0.15% by weight of the formulation;    -   Sodium benzoate, in about 0.15% by weight of the formulation;    -   Butylated hydroxytoluene, in about 0.10% by weight of the        formulation;    -   Stearyl glycyrrhetinate, in about 0.10% by weight of the        formulation;    -   Xanthan gum, in about 0.10% by weight of the formulation;    -   Disodium EDTA, in about 0.10% by weight of the formulation; and    -   Sodium hydroxide, in about 0.04% by weight of the formulation.

In certain embodiments, the invention relates to a formulation,consisting of:

-   -   any one of the aforementioned microemulsions, in about 55.19% by        weight of the formulation;    -   retinol, in about 1.33% by weight of the formulation;    -   isononyl isononanoate, in about 6.00% by weight of the        formulation;    -   cetyl alcohol, glyceryl stearate, PEG-75 stearate, ceteth-20,        and steareth-20, taken together, in about 5.00% by weight of the        formulation;    -   pentylene glycol, in about 0.25% by weight of the formulation;    -   C₁₂-C₁₅ alkyl ethylhexanoates, in about 4.00% by weight of the        formulation;    -   Palmitoyl-lysyl-valyl-lysine bistrifluoroacetate and glycerin,        taken together, in about 2.50% by weight of the formulation;    -   Jojoba wax, sunflower wax, and mimosa wax, taken together, in        about 2.00% by weight of the formulation;    -   Shea butter, in about 2.00% by weight of the formulation;    -   Caprylic/capric triglyceride, in about 2.00% by weight of the        formulation;    -   Polydimethylsiloxane, in about 1.50% by weight of the        formulation;    -   Dimethicone/divinyldimethicone/silsesquioxane cross polymer, in        about 1.50% by weight of the formulation;    -   Dipalmitoyl hydroxyproline, in about 1.00% by weight of the        formulation;    -   Cetyl alcohol, in about 1.00% by weight of the formulation;    -   Sodium hyaluronate, in about 0.01% by weight of the formulation;    -   Panthenol, in about 1.00% by weight of the formulation;    -   Niacinamide, in about 1.00% by weight of the formulation;    -   Butylene glycol and hydrolyzed rice extract, taken together, in        about 1.00% by weight of the formulation;    -   Algae extract and mugwort extract, taken together, in about        1.00% by weight of the formulation;    -   Glycerin, palmitoyl dipeptide-5 diaminobutyloyl        hydroxythreonine, and palmitoyl dipeptide-6        diaminohydroxybutyrate, taken together, in about 1.00% by weight        of the formulation;    -   Magnesium aluminum silicate, in about 0.60% by weight of the        formulation;    -   Tocopheryl acetate, in about 0.50% by weight of the formulation;    -   Tetrahexyldecyl ascorbate, in about 0.50% by weight of the        formulation;    -   Allantoin, in about 0.40% by weight of the formulation;    -   Bergamot, in about 0.30% by weight of the formulation;    -   (3-(4-chlorophenoxy)-2-hydroxypropyl)carbamate, in about 0.30%        by weight of the formulation;    -   Sodium ascorbate, in about 0.24% by weight of the formulation;    -   Bisabolol, in about 0.20% by weight of the formulation;    -   Tocopherol, in about 0.16% by weight of the formulation;    -   Potassium sorbate, in about 0.15% by weight of the formulation;    -   Sodium benzoate, in about 0.15% by weight of the formulation;    -   Butylated hydroxytoluene, in about 0.10% by weight of the        formulation;    -   Stearyl glycyrrhetinate, in about 0.10% by weight of the        formulation;    -   Xanthan gum, in about 0.10% by weight of the formulation;    -   Disodium EDTA, in about 0.10% by weight of the formulation; and    -   Sodium hydroxide, in about 0.04% by weight of the formulation.

In certain embodiments, the invention relates to a formulation,comprising:

-   -   any one of the aforementioned microemulsions, in about 54.92% by        weight of the formulation;    -   retinol, in about 1.20% by weight of the formulation;    -   isononyl isononanoate, in about 6.00% by weight of the        formulation;    -   cetyl alcohol, glyceryl stearate, PEG-75 stearate, ceteth-20,        and steareth-20, taken together, in about 5.00% by weight of the        formulation;    -   pentylene glycol, in about 0.25% by weight of the formulation;    -   C₁₂-C₁₅ alkyl ethylhexanoates, in about 4.00% by weight of the        formulation;    -   Palmitoyl-lysyl-valyl-lysine bistrifluoroacetate and glycerin,        taken together, in about 2.50% by weight of the formulation;    -   Jojoba wax, sunflower wax, and mimosa wax, taken together, in        about 2.00% by weight of the formulation;    -   Shea butter, in about 2.00% by weight of the formulation;    -   Caprylic/capric triglyceride, in about 2.00% by weight of the        formulation;    -   Polydimethylsiloxane, in about 1.50% by weight of the        formulation;    -   Dimethicone/divinyldimethicone/silsesquioxane cross polymer, in        about 1.50% by weight of the formulation;    -   Dipalmitoyl hydroxyproline, in about 1.00% by weight of the        formulation;    -   Cetyl alcohol, in about 1.00% by weight of the formulation;    -   Sodium hyaluronate, in about 0.01% by weight of the formulation;    -   Panthenol, in about 1.00% by weight of the formulation;    -   Niacinamide, in about 1.00% by weight of the formulation;    -   Butylene glycol and hydrolyzed rice extract, taken together, in        about 1.00% by weight of the formulation;    -   Algae extract and mugwort extract, taken together, in about        1.00% by weight of the formulation;    -   Glycerin, palmitoyl dipeptide-5 diaminobutyloyl        hydroxythreonine, and palmitoyl dipeptide-6        diaminohydroxybutyrate, taken together, in about 1.00% by weight        of the formulation;    -   Magnesium aluminum silicate, in about 1.00% by weight of the        formulation;    -   Tocopheryl acetate, in about 0.50% by weight of the formulation;    -   Tetrahexyldecyl ascorbate, in about 0.50% by weight of the        formulation;    -   Allantoin, in about 0.40% by weight of the formulation;    -   Bergamot, in about 0.30% by weight of the formulation;    -   (3-(4-chlorophenoxy)-2-hydroxypropyl)carbamate, in about 0.30%        by weight of the formulation;    -   Sodium ascorbate, in about 0.24% by weight of the formulation;    -   Bisabolol, in about 0.20% by weight of the formulation;    -   Tocopherol, in about 0.16% by weight of the formulation;    -   Potassium sorbate, in about 0.15% by weight of the formulation;    -   Sodium benzoate, in about 0.15% by weight of the formulation;    -   Butylated hydroxytoluene, in about 0.10% by weight of the        formulation;    -   Stearyl glycyrrhetinate, in about 0.10% by weight of the        formulation;    -   Xanthan gum, in about 0.10% by weight of the formulation;    -   Disodium EDTA, in about 0.10% by weight of the formulation; and    -   Sodium hydroxide, in about 0.04% by weight of the formulation.

In certain embodiments, the invention relates to a formulation,consisting essentially of:

-   -   any one of the aforementioned microemulsions, in about 54.92% by        weight of the formulation;    -   retinol, in about 1.20% by weight of the formulation;    -   isononyl isononanoate, in about 6.00% by weight of the        formulation;    -   cetyl alcohol, glyceryl stearate, PEG-75 stearate, ceteth-20,        and steareth-20, taken together, in about 5.00% by weight of the        formulation;    -   pentylene glycol, in about 0.25% by weight of the formulation;    -   C₁₂-C₁₅ alkyl ethylhexanoates, in about 4.00% by weight of the        formulation;    -   Palmitoyl-lysyl-valyl-lysine bistrifluoroacetate and glycerin,        taken together, in about 2.50% by weight of the formulation;    -   Jojoba wax, sunflower wax, and mimosa wax, taken together, in        about 2.00% by weight of the formulation;    -   Shea butter, in about 2.00% by weight of the formulation;    -   Caprylic/capric triglyceride, in about 2.00% by weight of the        formulation;    -   Polydimethylsiloxane, in about 1.50% by weight of the        formulation;    -   Dimethicone/divinyldimethicone/silsesquioxane cross polymer, in        about 1.50% by weight of the formulation;    -   Dipalmitoyl hydroxyproline, in about 1.00% by weight of the        formulation;    -   Cetyl alcohol, in about 1.00% by weight of the formulation;    -   Sodium hyaluronate, in about 0.01% by weight of the formulation;    -   Panthenol, in about 1.00% by weight of the formulation;    -   Niacinamide, in about 1.00% by weight of the formulation;    -   Butylene glycol and hydrolyzed rice extract, taken together, in        about 1.00% by weight of the formulation;    -   Algae extract and mugwort extract, taken together, in about        1.00% by weight of the formulation;    -   Glycerin, palmitoyl dipeptide-5 diaminobutyloyl        hydroxythreonine, and palmitoyl dipeptide-6        diaminohydroxybutyrate, taken together, in about 1.00% by weight        of the formulation;    -   Magnesium aluminum silicate, in about 1.00% by weight of the        formulation;    -   Tocopheryl acetate, in about 0.50% by weight of the formulation;    -   Tetrahexyldecyl ascorbate, in about 0.50% by weight of the        formulation;    -   Allantoin, in about 0.40% by weight of the formulation;    -   Bergamot, in about 0.30% by weight of the formulation;    -   (3-(4-chlorophenoxy)-2-hydroxypropyl)carbamate, in about 0.30%        by weight of the formulation;    -   Sodium ascorbate, in about 0.24% by weight of the formulation;    -   Bisabolol, in about 0.20% by weight of the formulation;    -   Tocopherol, in about 0.16% by weight of the formulation;    -   Potassium sorbate, in about 0.15% by weight of the formulation;    -   Sodium benzoate, in about 0.15% by weight of the formulation;    -   Butylated hydroxytoluene, in about 0.10% by weight of the        formulation;    -   Stearyl glycyrrhetinate, in about 0.10% by weight of the        formulation;    -   Xanthan gum, in about 0.10% by weight of the formulation;    -   Disodium EDTA, in about 0.10% by weight of the formulation; and    -   Sodium hydroxide, in about 0.04% by weight of the formulation.

In certain embodiments, the invention relates to a formulation,consisting of: any one of the aforementioned microemulsions, in about54.92% by weight of the formulation;

-   -   retinol, in about 1.20% by weight of the formulation;    -   isononyl isononanoate, in about 6.00% by weight of the        formulation;    -   cetyl alcohol, glyceryl stearate, PEG-75 stearate, ceteth-20,        and steareth-20, taken together, in about 5.00% by weight of the        formulation;    -   pentylene glycol, in about 0.25% by weight of the formulation;    -   C₁₂-C₁₅ alkyl ethylhexanoates, in about 4.00% by weight of the        formulation;    -   Palmitoyl-lysyl-valyl-lysine bistrifluoroacetate and glycerin,        taken together, in about 2.50% by weight of the formulation;    -   Jojoba wax, sunflower wax, and mimosa wax, taken together, in        about 2.00% by weight of the formulation;    -   Shea butter, in about 2.00% by weight of the formulation;    -   Caprylic/capric triglyceride, in about 2.00% by weight of the        formulation;    -   Polydimethylsiloxane, in about 1.50% by weight of the        formulation;    -   Dimethicone/divinyldimethicone/silsesquioxane cross polymer, in        about 1.50% by weight of the formulation;    -   Dipalmitoyl hydroxyproline, in about 1.00% by weight of the        formulation;    -   Cetyl alcohol, in about 1.00% by weight of the formulation;    -   Sodium hyaluronate, in about 0.01% by weight of the formulation;    -   Panthenol, in about 1.00% by weight of the formulation;    -   Niacinamide, in about 1.00% by weight of the formulation;    -   Butylene glycol and hydrolyzed rice extract, taken together, in        about 1.00% by weight of the formulation;    -   Algae extract and mugwort extract, taken together, in about        1.00% by weight of the formulation;    -   Glycerin, palmitoyl dipeptide-5 diaminobutyloyl        hydroxythreonine, and palmitoyl dipeptide-6        diaminohydroxybutyrate, taken together, in about 1.00% by weight        of the formulation;    -   Magnesium aluminum silicate, in about 1.00% by weight of the        formulation;    -   Tocopheryl acetate, in about 0.50% by weight of the formulation;    -   Tetrahexyldecyl ascorbate, in about 0.50% by weight of the        formulation;    -   Allantoin, in about 0.40% by weight of the formulation;    -   Bergamot, in about 0.30% by weight of the formulation;    -   (3-(4-chlorophenoxy)-2-hydroxypropyl)carbamate, in about 0.30%        by weight of the formulation;    -   Sodium ascorbate, in about 0.24% by weight of the formulation;    -   Bisabolol, in about 0.20% by weight of the formulation;    -   Tocopherol, in about 0.16% by weight of the formulation;    -   Potassium sorbate, in about 0.15% by weight of the formulation;    -   Sodium benzoate, in about 0.15% by weight of the formulation;    -   Butylated hydroxytoluene, in about 0.10% by weight of the        formulation;    -   Stearyl glycyrrhetinate, in about 0.10% by weight of the        formulation;    -   Xanthan gum, in about 0.10% by weight of the formulation;    -   Disodium EDTA, in about 0.10% by weight of the formulation; and    -   Sodium hydroxide, in about 0.04% by weight of the formulation.

In certain embodiments, the invention relates to a formulation,comprising:

-   -   any one of the aforementioned microemulsions, in about 55.94% by        weight of the formulation;    -   retinol, in about 0.18% by weight of the formulation;    -   isononyl isononanoate, in about 6.00% by weight of the        formulation;    -   cetyl alcohol, glyceryl stearate, PEG-75 stearate, ceteth-20,        and steareth-20, taken together, in about 5.00% by weight of the        formulation;    -   pentylene glycol, in about 0.25% by weight of the formulation;    -   C₁₂-C₁₅ alkyl ethylhexanoates, in about 4.00% by weight of the        formulation;    -   Palmitoyl-lysyl-valyl-lysine bistrifluoroacetate and glycerin,        taken together, in about 2.50% by weight of the formulation;    -   Jojoba wax, sunflower wax, and mimosa wax, taken together, in        about 2.00% by weight of the formulation;    -   Shea butter, in about 2.00% by weight of the formulation;    -   Caprylic/capric triglyceride, in about 2.00% by weight of the        formulation;    -   Polydimethylsiloxane, in about 1.50% by weight of the        formulation;    -   Dimethicone/divinyldimethicone/silsesquioxane cross polymer, in        about 1.50% by weight of the formulation;    -   Dipalmitoyl hydroxyproline, in about 1.00% by weight of the        formulation;    -   Cetyl alcohol, in about 1.00% by weight of the formulation;    -   Sodium hyaluronate, in about 0.01% by weight of the formulation;    -   Panthenol, in about 1.00% by weight of the formulation;    -   Niacinamide, in about 1.00% by weight of the formulation;    -   Butylene glycol and hydrolyzed rice extract, taken together, in        about 1.00% by weight of the formulation;    -   Algae extract and mugwort extract, taken together, in about        1.00% by weight of the formulation;    -   Glycerin, palmitoyl dipeptide-5 diaminobutyloyl        hydroxythreonine, and palmitoyl dipeptide-6        diaminohydroxybutyrate, taken together, in about 1.00% by weight        of the formulation;    -   Magnesium aluminum silicate, in about 1.00% by weight of the        formulation;    -   Tocopheryl acetate, in about 0.50% by weight of the formulation;    -   Tetrahexyldecyl ascorbate, in about 0.50% by weight of the        formulation;    -   Allantoin, in about 0.40% by weight of the formulation;    -   Bergamot, in about 0.30% by weight of the formulation;    -   (3-(4-chlorophenoxy)-2-hydroxypropyl)carbamate, in about 0.30%        by weight of the formulation;    -   Sodium ascorbate, in about 0.24% by weight of the formulation;    -   Bisabolol, in about 0.20% by weight of the formulation;    -   Tocopherol, in about 0.16% by weight of the formulation;    -   Potassium sorbate, in about 0.15% by weight of the formulation;    -   Sodium benzoate, in about 0.15% by weight of the formulation;    -   Butylated hydroxytoluene, in about 0.10% by weight of the        formulation;    -   Stearyl glycyrrhetinate, in about 0.10% by weight of the        formulation;    -   Xanthan gum, in about 0.10% by weight of the formulation;    -   Disodium EDTA, in about 0.10% by weight of the formulation; and    -   Sodium hydroxide, in about 0.04% by weight of the formulation.

In certain embodiments, the invention relates to a formulation,consisting essentially of:

-   -   any one of the aforementioned microemulsions, in about 55.94% by        weight of the formulation;    -   retinol, in about 0.18% by weight of the formulation;    -   isononyl isononanoate, in about 6.00% by weight of the        formulation;    -   cetyl alcohol, glyceryl stearate, PEG-75 stearate, ceteth-20,        and steareth-20, taken together, in about 5.00% by weight of the        formulation;    -   pentylene glycol, in about 0.25% by weight of the formulation;    -   C₁₂-C₁₅ alkyl ethylhexanoates, in about 4.00% by weight of the        formulation;    -   Palmitoyl-lysyl-valyl-lysine bistrifluoroacetate and glycerin,        taken together, in about 2.50% by weight of the formulation;    -   Jojoba wax, sunflower wax, and mimosa wax, taken together, in        about 2.00% by weight of the formulation;    -   Shea butter, in about 2.00% by weight of the formulation;    -   Caprylic/capric triglyceride, in about 2.00% by weight of the        formulation;    -   Polydimethylsiloxane, in about 1.50% by weight of the        formulation;    -   Dimethicone/divinyldimethicone/silsesquioxane cross polymer, in        about 1.50% by weight of the formulation;    -   Dipalmitoyl hydroxyproline, in about 1.00% by weight of the        formulation;    -   Cetyl alcohol, in about 1.00% by weight of the formulation;    -   Sodium hyaluronate, in about 0.01% by weight of the formulation;    -   Panthenol, in about 1.00% by weight of the formulation;    -   Niacinamide, in about 1.00% by weight of the formulation;    -   Butylene glycol and hydrolyzed rice extract, taken together, in        about 1.00% by weight of the formulation;    -   Algae extract and mugwort extract, taken together, in about        1.00% by weight of the formulation;    -   Glycerin, palmitoyl dipeptide-5 diaminobutyloyl        hydroxythreonine, and palmitoyl dipeptide-6        diaminohydroxybutyrate, taken together, in about 1.00% by weight        of the formulation;    -   Magnesium aluminum silicate, in about 1.00% by weight of the        formulation;    -   Tocopheryl acetate, in about 0.50% by weight of the formulation;    -   Tetrahexyldecyl ascorbate, in about 0.50% by weight of the        formulation;    -   Allantoin, in about 0.40% by weight of the formulation;    -   Bergamot, in about 0.30% by weight of the formulation;    -   (3-(4-chlorophenoxy)-2-hydroxypropyl)carbamate, in about 0.30%        by weight of the formulation;    -   Sodium ascorbate, in about 0.24% by weight of the formulation;    -   Bisabolol, in about 0.20% by weight of the formulation;    -   Tocopherol, in about 0.16% by weight of the formulation;    -   Potassium sorbate, in about 0.15% by weight of the formulation;    -   Sodium benzoate, in about 0.15% by weight of the formulation;    -   Butylated hydroxytoluene, in about 0.10% by weight of the        formulation;    -   Stearyl glycyrrhetinate, in about 0.10% by weight of the        formulation;    -   Xanthan gum, in about 0.10% by weight of the formulation;    -   Disodium EDTA, in about 0.10% by weight of the formulation; and    -   Sodium hydroxide, in about 0.04% by weight of the formulation.

In certain embodiments, the invention relates to a formulation,consisting of:

-   -   any one of the aforementioned microemulsions, in about 55.94% by        weight of the formulation;    -   retinol, in about 0.18% by weight of the formulation;    -   isononyl isononanoate, in about 6.00% by weight of the        formulation;    -   cetyl alcohol, glyceryl stearate, PEG-75 stearate, ceteth-20,        and steareth-20, taken together, in about 5.00% by weight of the        formulation;    -   pentylene glycol, in about 0.25% by weight of the formulation;    -   C₁₂-C₁₅ alkyl ethylhexanoates, in about 4.00% by weight of the        formulation;    -   Palmitoyl-lysyl-valyl-lysine bistrifluoroacetate and glycerin,        taken together, in about 2.50% by weight of the formulation;    -   Jojoba wax, sunflower wax, and mimosa wax, taken together, in        about 2.00% by weight of the formulation;    -   Shea butter, in about 2.00% by weight of the formulation;    -   Caprylic/capric triglyceride, in about 2.00% by weight of the        formulation;    -   Polydimethylsiloxane, in about 1.50% by weight of the        formulation;    -   Dimethicone/divinyldimethicone/silsesquioxane cross polymer, in        about 1.50% by weight of the formulation;    -   Dipalmitoyl hydroxyproline, in about 1.00% by weight of the        formulation;    -   Cetyl alcohol, in about 1.00% by weight of the formulation;    -   Sodium hyaluronate, in about 0.01% by weight of the formulation;    -   Panthenol, in about 1.00% by weight of the formulation;    -   Niacinamide, in about 1.00% by weight of the formulation;    -   Butylene glycol and hydrolyzed rice extract, taken together, in        about 1.00% by weight of the formulation;    -   Algae extract and mugwort extract, taken together, in about        1.00% by weight of the formulation;    -   Glycerin, palmitoyl dipeptide-5 diaminobutyloyl        hydroxythreonine, and palmitoyl dipeptide-6        diaminohydroxybutyrate, taken together, in about 1.00% by weight        of the formulation;    -   Magnesium aluminum silicate, in about 1.00% by weight of the        formulation;    -   Tocopheryl acetate, in about 0.50% by weight of the formulation;    -   Tetrahexyldecyl ascorbate, in about 0.50% by weight of the        formulation;    -   Allantoin, in about 0.40% by weight of the formulation;    -   Bergamot, in about 0.30% by weight of the formulation;    -   (3-(4-chlorophenoxy)-2-hydroxypropyl)carbamate, in about 0.30%        by weight of the formulation;    -   Sodium ascorbate, in about 0.24% by weight of the formulation;    -   Bisabolol, in about 0.20% by weight of the formulation;    -   Tocopherol, in about 0.16% by weight of the formulation;    -   Potassium sorbate, in about 0.15% by weight of the formulation;    -   Sodium benzoate, in about 0.15% by weight of the formulation;    -   Butylated hydroxytoluene, in about 0.10% by weight of the        formulation;    -   Stearyl glycyrrhetinate, in about 0.10% by weight of the        formulation;    -   Xanthan gum, in about 0.10% by weight of the formulation;    -   Disodium EDTA, in about 0.10% by weight of the formulation; and    -   Sodium hydroxide, in about 0.04% by weight of the formulation.

In certain embodiments, the invention relates to a formulation,comprising:

-   -   any one of the aforementioned microemulsions, in about 57.82% by        weight of the formulation;    -   retinol, in about 1.20% by weight of the formulation;    -   isononyl isononanoate, in about 4.00% by weight of the        formulation;    -   cetyl alcohol, glyceryl stearate, PEG-75 stearate, ceteth-20,        and steareth-20, taken together, in about 5.00% by weight of the        formulation;    -   pentylene glycol, in about 0.25% by weight of the formulation;    -   C₁₂-C₁₅ alkyl ethylhexanoates, in about 2.00% by weight of the        formulation;    -   Palmitoyl-lysyl-valyl-lysine bistrifluoroacetate and glycerin,        taken together, in about 2.50% by weight of the formulation;    -   Jojoba wax, sunflower wax, and mimosa wax, taken together, in        about 2.00% by weight of the formulation;    -   Shea butter, in about 2.00% by weight of the formulation;    -   Caprylic/capric triglyceride, in about 2.00% by weight of the        formulation;    -   Polydimethylsiloxane, in about 1.50% by weight of the        formulation;    -   Dimethicone/divinyldimethicone/silsesquioxane cross polymer, in        about 1.50% by weight of the formulation;    -   Dipalmitoyl hydroxyproline, in about 1.00% by weight of the        formulation;    -   Cetyl alcohol, in about 1.50% by weight of the formulation;    -   Sodium hyaluronate, in about 0.01% by weight of the formulation;    -   Panthenol, in about 1.00% by weight of the formulation;    -   Niacinamide, in about 1.00% by weight of the formulation;    -   Butylene glycol and hydrolyzed rice extract, taken together, in        about 1.00% by weight of the formulation;    -   Algae extract and mugwort extract, taken together, in about        1.00% by weight of the formulation;    -   Glycerin, palmitoyl dipeptide-5 diaminobutyloyl        hydroxythreonine, and palmitoyl dipeptide-6        diaminohydroxybutyrate, taken together, in about 1.00% by weight        of the formulation;    -   Magnesium aluminum silicate, in about 1.50% by weight of the        formulation;    -   Tocopheryl acetate, in about 0.50% by weight of the formulation;    -   Tetrahexyldecyl ascorbate, in about 0.50% by weight of the        formulation;    -   Allantoin, in about 0.40% by weight of the formulation;    -   Bergamot, in about 0.30% by weight of the formulation;    -   (3-(4-chlorophenoxy)-2-hydroxypropyl)carbamate, in about 0.30%        by weight of the formulation;    -   Sodium ascorbate, in about 0.24% by weight of the formulation;    -   Bisabolol, in about 0.20% by weight of the formulation;    -   Tocopherol, in about 0.16% by weight of the formulation;    -   Potassium sorbate, in about 0.15% by weight of the formulation;    -   Sodium benzoate, in about 0.15% by weight of the formulation;    -   Butylated hydroxytoluene, in about 0.10% by weight of the        formulation;    -   Stearyl glycyrrhetinate, in about 0.10% by weight of the        formulation;    -   Xanthan gum, in about 0.20% by weight of the formulation;    -   Disodium EDTA, in about 0.10% by weight of the formulation; and    -   Sodium hydroxide, in about 0.04% by weight of the formulation.

In certain embodiments, the invention relates to a formulation,consisting essentially of:

-   -   any one of the aforementioned microemulsions, in about 57.82% by        weight of the formulation;    -   retinol, in about 1.20% by weight of the formulation;    -   isononyl isononanoate, in about 4.00% by weight of the        formulation;    -   cetyl alcohol, glyceryl stearate, PEG-75 stearate, ceteth-20,        and steareth-20, taken together, in about 5.00% by weight of the        formulation;    -   pentylene glycol, in about 0.25% by weight of the formulation;    -   C₁₂-C₁₅ alkyl ethylhexanoates, in about 2.00% by weight of the        formulation;    -   Palmitoyl-lysyl-valyl-lysine bistrifluoroacetate and glycerin,        taken together, in about 2.50% by weight of the formulation;    -   Jojoba wax, sunflower wax, and mimosa wax, taken together, in        about 2.00% by weight of the formulation;    -   Shea butter, in about 2.00% by weight of the formulation;    -   Caprylic/capric triglyceride, in about 2.00% by weight of the        formulation;    -   Polydimethylsiloxane, in about 1.50% by weight of the        formulation;    -   Dimethicone/divinyldimethicone/silsesquioxane cross polymer, in        about 1.50% by weight of the formulation;    -   Dipalmitoyl hydroxyproline, in about 1.00% by weight of the        formulation;    -   Cetyl alcohol, in about 1.50% by weight of the formulation;    -   Sodium hyaluronate, in about 0.01% by weight of the formulation;    -   Panthenol, in about 1.00% by weight of the formulation;    -   Niacinamide, in about 1.00% by weight of the formulation;    -   Butylene glycol and hydrolyzed rice extract, taken together, in        about 1.00% by weight of the formulation;    -   Algae extract and mugwort extract, taken together, in about        1.00% by weight of the formulation;    -   Glycerin, palmitoyl dipeptide-5 diaminobutyloyl        hydroxythreonine, and palmitoyl dipeptide-6        diaminohydroxybutyrate, taken together, in about 1.00% by weight        of the formulation;    -   Magnesium aluminum silicate, in about 1.50% by weight of the        formulation;    -   Tocopheryl acetate, in about 0.50% by weight of the formulation;    -   Tetrahexyldecyl ascorbate, in about 0.50% by weight of the        formulation;    -   Allantoin, in about 0.40% by weight of the formulation;    -   Bergamot, in about 0.30% by weight of the formulation;    -   (3-(4-chlorophenoxy)-2-hydroxypropyl)carbamate, in about 0.30%        by weight of the formulation;    -   Sodium ascorbate, in about 0.24% by weight of the formulation;    -   Bisabolol, in about 0.20% by weight of the formulation;    -   Tocopherol, in about 0.16% by weight of the formulation;    -   Potassium sorbate, in about 0.15% by weight of the formulation;    -   Sodium benzoate, in about 0.15% by weight of the formulation;    -   Butylated hydroxytoluene, in about 0.10% by weight of the        formulation;    -   Stearyl glycyrrhetinate, in about 0.10% by weight of the        formulation;    -   Xanthan gum, in about 0.20% by weight of the formulation;    -   Disodium EDTA, in about 0.10% by weight of the formulation; and    -   Sodium hydroxide, in about 0.04% by weight of the formulation.

In certain embodiments, the invention relates to a formulation,consisting of:

-   -   any one of the aforementioned microemulsions, in about 57.82% by        weight of the formulation;    -   retinol, in about 1.20% by weight of the formulation;    -   isononyl isononanoate, in about 4.00% by weight of the        formulation;    -   cetyl alcohol, glyceryl stearate, PEG-75 stearate, ceteth-20,        and steareth-20, taken together, in about 5.00% by weight of the        formulation;    -   pentylene glycol, in about 0.25% by weight of the formulation;    -   C₁₂-C₁₅ alkyl ethylhexanoates, in about 2.00% by weight of the        formulation;    -   Palmitoyl-lysyl-valyl-lysine bistrifluoroacetate and glycerin,        taken together, in about 2.50% by weight of the formulation;    -   Jojoba wax, sunflower wax, and mimosa wax, taken together, in        about 2.00% by weight of the formulation;    -   Shea butter, in about 2.00% by weight of the formulation;    -   Caprylic/capric triglyceride, in about 2.00% by weight of the        formulation;    -   Polydimethylsiloxane, in about 1.50% by weight of the        formulation;    -   Dimethicone/divinyldimethicone/silsesquioxane cross polymer, in        about 1.50% by weight of the formulation;    -   Dipalmitoyl hydroxyproline, in about 1.00% by weight of the        formulation;    -   Cetyl alcohol, in about 1.50% by weight of the formulation;    -   Sodium hyaluronate, in about 0.01% by weight of the formulation;    -   Panthenol, in about 1.00% by weight of the formulation;    -   Niacinamide, in about 1.00% by weight of the formulation;    -   Butylene glycol and hydrolyzed rice extract, taken together, in        about 1.00% by weight of the formulation;    -   Algae extract and mugwort extract, taken together, in about        1.00% by weight of the formulation;    -   Glycerin, palmitoyl dipeptide-5 diaminobutyloyl        hydroxythreonine, and palmitoyl dipeptide-6        diaminohydroxybutyrate, taken together, in about 1.00% by weight        of the formulation;    -   Magnesium aluminum silicate, in about 1.50% by weight of the        formulation;    -   Tocopheryl acetate, in about 0.50% by weight of the formulation;    -   Tetrahexyldecyl ascorbate, in about 0.50% by weight of the        formulation;    -   Allantoin, in about 0.40% by weight of the formulation;    -   Bergamot, in about 0.30% by weight of the formulation;    -   (3-(4-chlorophenoxy)-2-hydroxypropyl)carbamate, in about 0.30%        by weight of the formulation;    -   Sodium ascorbate, in about 0.24% by weight of the formulation;    -   Bisabolol, in about 0.20% by weight of the formulation;    -   Tocopherol, in about 0.16% by weight of the formulation;    -   Potassium sorbate, in about 0.15% by weight of the formulation;    -   Sodium benzoate, in about 0.15% by weight of the formulation;    -   Butylated hydroxytoluene, in about 0.10% by weight of the        formulation;    -   Stearyl glycyrrhetinate, in about 0.10% by weight of the        formulation;    -   Xanthan gum, in about 0.20% by weight of the formulation;    -   Disodium EDTA, in about 0.10% by weight of the formulation; and    -   Sodium hydroxide, in about 0.04% by weight of the formulation.

In certain embodiments, the invention relates to a formulation,comprising:

-   -   any one of the aforementioned microemulsions, in about 58.84% by        weight of the formulation;    -   retinol, in about 0.18% by weight of the formulation;    -   isononyl isononanoate, in about 4.00% by weight of the        formulation;    -   cetyl alcohol, glyceryl stearate, PEG-75 stearate, ceteth-20,        and steareth-20, taken together, in about 5.00% by weight of the        formulation;    -   pentylene glycol, in about 0.25% by weight of the formulation;    -   C₁₂-C₁₅ alkyl ethylhexanoates, in about 2.00% by weight of the        formulation;    -   Palmitoyl-lysyl-valyl-lysine bistrifluoroacetate and glycerin,        taken together, in about 2.50% by weight of the formulation;    -   Jojoba wax, sunflower wax, and mimosa wax, taken together, in        about 2.00% by weight of the formulation;    -   Shea butter, in about 2.00% by weight of the formulation;    -   Caprylic/capric triglyceride, in about 2.00% by weight of the        formulation;    -   Polydimethylsiloxane, in about 1.50% by weight of the        formulation;    -   Dimethicone/divinyldimethicone/silsesquioxane cross polymer, in        about 1.50% by weight of the formulation;    -   Dipalmitoyl hydroxyproline, in about 1.00% by weight of the        formulation;    -   Cetyl alcohol, in about 1.50% by weight of the formulation;    -   Sodium hyaluronate, in about 0.01% by weight of the formulation;    -   Panthenol, in about 1.00% by weight of the formulation;    -   Niacinamide, in about 1.00% by weight of the formulation;    -   Butylene glycol and hydrolyzed rice extract, taken together, in        about 1.00% by weight of the formulation;    -   Algae extract and mugwort extract, taken together, in about        1.00% by weight of the formulation;    -   Glycerin, palmitoyl dipeptide-5 diaminobutyloyl        hydroxythreonine, and palmitoyl dipeptide-6        diaminohydroxybutyrate, taken together, in about 1.00% by weight        of the formulation;    -   Magnesium aluminum silicate, in about 1.50% by weight of the        formulation;    -   Tocopheryl acetate, in about 0.50% by weight of the formulation;    -   Tetrahexyldecyl ascorbate, in about 0.50% by weight of the        formulation;    -   Allantoin, in about 0.40% by weight of the formulation;    -   Bergamot, in about 0.30% by weight of the formulation;    -   (3-(4-chlorophenoxy)-2-hydroxypropyl)carbamate, in about 0.30%        by weight of the formulation;    -   Sodium ascorbate, in about 0.24% by weight of the formulation;    -   Bisabolol, in about 0.20% by weight of the formulation;    -   Tocopherol, in about 0.16% by weight of the formulation;    -   Potassium sorbate, in about 0.15% by weight of the formulation;    -   Sodium benzoate, in about 0.15% by weight of the formulation;    -   Butylated hydroxytoluene, in about 0.10% by weight of the        formulation;    -   Stearyl glycyrrhetinate, in about 0.10% by weight of the        formulation;    -   Xanthan gum, in about 0.20% by weight of the formulation;    -   Disodium EDTA, in about 0.10% by weight of the formulation; and    -   Sodium hydroxide, in about 0.04% by weight of the formulation.

In certain embodiments, the invention relates to a formulation,consisting essentially of:

-   -   any one of the aforementioned microemulsions, in about 58.84% by        weight of the formulation;    -   retinol, in about 0.18% by weight of the formulation;    -   isononyl isononanoate, in about 4.00% by weight of the        formulation;    -   cetyl alcohol, glyceryl stearate, PEG-75 stearate, ceteth-20,        and steareth-20, taken together, in about 5.00% by weight of the        formulation;    -   pentylene glycol, in about 0.25% by weight of the formulation;    -   C₁₂-C₁₅ alkyl ethylhexanoates, in about 2.00% by weight of the        formulation;    -   Palmitoyl-lysyl-valyl-lysine bistrifluoroacetate and glycerin,        taken together, in about 2.50% by weight of the formulation;    -   Jojoba wax, sunflower wax, and mimosa wax, taken together, in        about 2.00% by weight of the formulation;    -   Shea butter, in about 2.00% by weight of the formulation;    -   Caprylic/capric triglyceride, in about 2.00% by weight of the        formulation;    -   Polydimethylsiloxane, in about 1.50% by weight of the        formulation;    -   Dimethicone/divinyldimethicone/silsesquioxane cross polymer, in        about 1.50% by weight of the formulation;    -   Dipalmitoyl hydroxyproline, in about 1.00% by weight of the        formulation;    -   Cetyl alcohol, in about 1.50% by weight of the formulation;    -   Sodium hyaluronate, in about 0.01% by weight of the formulation;    -   Panthenol, in about 1.00% by weight of the formulation;    -   Niacinamide, in about 1.00% by weight of the formulation;    -   Butylene glycol and hydrolyzed rice extract, taken together, in        about 1.00% by weight of the formulation;    -   Algae extract and mugwort extract, taken together, in about        1.00% by weight of the formulation;    -   Glycerin, palmitoyl dipeptide-5 diaminobutyloyl        hydroxythreonine, and palmitoyl dipeptide-6        diaminohydroxybutyrate, taken together, in about 1.00% by weight        of the formulation;    -   Magnesium aluminum silicate, in about 1.50% by weight of the        formulation;    -   Tocopheryl acetate, in about 0.50% by weight of the formulation;    -   Tetrahexyldecyl ascorbate, in about 0.50% by weight of the        formulation;    -   Allantoin, in about 0.40% by weight of the formulation;    -   Bergamot, in about 0.30% by weight of the formulation;    -   (3-(4-chlorophenoxy)-2-hydroxypropyl)carbamate, in about 0.30%        by weight of the formulation;    -   Sodium ascorbate, in about 0.24% by weight of the formulation;    -   Bisabolol, in about 0.20% by weight of the formulation;    -   Tocopherol, in about 0.16% by weight of the formulation;    -   Potassium sorbate, in about 0.15% by weight of the formulation;    -   Sodium benzoate, in about 0.15% by weight of the formulation;    -   Butylated hydroxytoluene, in about 0.10% by weight of the        formulation;    -   Stearyl glycyrrhetinate, in about 0.10% by weight of the        formulation;    -   Xanthan gum, in about 0.20% by weight of the formulation;    -   Disodium EDTA, in about 0.10% by weight of the formulation; and    -   Sodium hydroxide, in about 0.04% by weight of the formulation.

In certain embodiments, the invention relates to a formulation,consisting of:

-   -   any one of the aforementioned microemulsions, in about 58.84% by        weight of the formulation;    -   retinol, in about 0.18% by weight of the formulation;    -   isononyl isononanoate, in about 4.00% by weight of the        formulation;    -   cetyl alcohol, glyceryl stearate, PEG-75 stearate, ceteth-20,        and steareth-20, taken together, in about 5.00% by weight of the        formulation;    -   pentylene glycol, in about 0.25% by weight of the formulation;    -   C₁₂-C₁₅ alkyl ethylhexanoates, in about 2.00% by weight of the        formulation;    -   Palmitoyl-lysyl-valyl-lysine bistrifluoroacetate and glycerin,        taken together, in about 2.50% by weight of the formulation;    -   Jojoba wax, sunflower wax, and mimosa wax, taken together, in        about 2.00% by weight of the formulation;    -   Shea butter, in about 2.00% by weight of the formulation;    -   Caprylic/capric triglyceride, in about 2.00% by weight of the        formulation;    -   Polydimethylsiloxane, in about 1.50% by weight of the        formulation;    -   Dimethicone/divinyldimethicone/silsesquioxane cross polymer, in        about 1.50% by weight of the formulation;    -   Dipalmitoyl hydroxyproline, in about 1.00% by weight of the        formulation;    -   Cetyl alcohol, in about 1.50% by weight of the formulation;    -   Sodium hyaluronate, in about 0.01% by weight of the formulation;    -   Panthenol, in about 1.00% by weight of the formulation;    -   Niacinamide, in about 1.00% by weight of the formulation;    -   Butylene glycol and hydrolyzed rice extract, taken together, in        about 1.00% by weight of the formulation;    -   Algae extract and mugwort extract, taken together, in about        1.00% by weight of the formulation;    -   Glycerin, palmitoyl dipeptide-5 diaminobutyloyl        hydroxythreonine, and palmitoyl dipeptide-6        diaminohydroxybutyrate, taken together, in about 1.00% by weight        of the formulation;    -   Magnesium aluminum silicate, in about 1.50% by weight of the        formulation;    -   Tocopheryl acetate, in about 0.50% by weight of the formulation;    -   Tetrahexyldecyl ascorbate, in about 0.50% by weight of the        formulation;    -   Allantoin, in about 0.40% by weight of the formulation;    -   Bergamot, in about 0.30% by weight of the formulation;    -   (3-(4-chlorophenoxy)-2-hydroxypropyl)carbamate, in about 0.30%        by weight of the formulation;    -   Sodium ascorbate, in about 0.24% by weight of the formulation;    -   Bisabolol, in about 0.20% by weight of the formulation;    -   Tocopherol, in about 0.16% by weight of the formulation;    -   Potassium sorbate, in about 0.15% by weight of the formulation;    -   Sodium benzoate, in about 0.15% by weight of the formulation;    -   Butylated hydroxytoluene, in about 0.10% by weight of the        formulation;    -   Stearyl glycyrrhetinate, in about 0.10% by weight of the        formulation;    -   Xanthan gum, in about 0.20% by weight of the formulation;    -   Disodium EDTA, in about 0.10% by weight of the formulation; and    -   Sodium hydroxide, in about 0.04% by weight of the formulation.

Exemplary Components of the Formulation

As outlined above, in certain embodiments, the invention relates to aformulation. The components described below may be present in any one ofthe aforementioned formulations.

In certain embodiments, the invention relates to any one of theaforementioned formulations, wherein the active agent is selected fromthe group consisting of salicylic acid, papain, sulfur, glycolic acid,pyruvic acid, resorcinol, N-acetylcysteine, retinoids such as retinoicacid (e.g., tretinoin) and its derivatives (e.g., cis and trans isomers,esters), retinol, alpha hydroxy acids, beta hydroxy acids, coal tar, andcombinations thereof.

In certain embodiments, the invention relates to any one of theaforementioned formulations, wherein the active agent is retinol.

In certain embodiments, the invention relates to any one of theaforementioned formulations, wherein the retinol is stabilized by themicroemulsion. In certain embodiments, the invention relates to any oneof the aforementioned formulations, wherein the retinol is encapsulatedin the microemulsion.

In certain embodiments, the invention relates to any one of theaforementioned formulations, wherein the active agent is substantiallywater insoluble.

In certain embodiments, the invention relates to any one of theaforementioned formulations wherein the active agent is present in anamount from about 0.01% to about 5% by weight of the formulation. Incertain embodiments, the invention relates to any one of theaforementioned formulations, wherein the active agent is present inabout 0.01%, about 0.02%, about 0.04%, about 0.06%, about 0.08%, about0.1%, about 0.2%, about 0.3%, about 0.4%, about 0.5%, about 0.6%, about0.7%, about 0.8%, about 0.9%, about 1.0%, about 1.2%, about 1.4%, about1.6%, about 1.8%, about 2.0%, about 2.2%, about 2.4%, about 2.6%, about2.8%, about 3.0%, about 3.5%, about 4.0%, about 4.5%, or about 5.0% byweight of the formulation.

In certain embodiments, the invention relates to any one of theaforementioned formulations, wherein the active agent is present inabout 0.06% by weight of the formulation. In certain embodiments, theinvention relates to any one of the aforementioned formulations, whereinthe active agent is present in about 1.2% by weight of the formulation.

In certain embodiments, the invention relates to any one of theaforementioned formulations wherein retinol is present in an amount fromabout 0.01% to about 5% by weight of the formulation. In certainembodiments, the invention relates to any one of the aforementionedformulations, wherein retinol is present in about 0.01%, about 0.02%,about 0.04%, about 0.06%, about 0.08%, about 0.1%, about 0.2%, about0.3%, about 0.4%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, about0.9%, about 1.0%, about 1.2%, about 1.4%, about 1.6%, about 1.8%, about2.0%, about 2.2%, about 2.4%, about 2.6%, about 2.8%, about 3.0%, about3.5%, about 4.0%, about 4.5%, or about 5.0% by weight of theformulation. In certain embodiments, the invention relates to any one ofthe aforementioned formulations, wherein retinol is present in about0.06% by weight of the formulation. In certain embodiments, theinvention relates to any one of the aforementioned formulations, whereinretinol is present in about 1.2% by weight of the formulation.

In certain embodiments, the invention relates to any one of theaforementioned formulations, wherein the third surfactant is selectedfrom the group consisting of: cetyl alcohol, Polysorbate 20, Polysorbate40, Polysorbate 60, Polysorbate 80, steareth-10 (Brij 76), sodiumdodecyl sulfate (sodium lauryl sulfate), lauryl dimethyl amine oxide,cetyltrimethylammonium bromide (CTAB), polyethoxylated alcohols,polyoxyethylene sorbitan, octoxynol, N,N-dimethyldodecylamine-N-oxide,hexadecyltrimethylammonium bromide (HTAB), polyoxyl 10 lauryl ether,bile salts (such as sodium deoxycholate or sodium cholate), polyoxylcastor oil, nonylphenol ethoxylate, cyclodextrins, lecithin, dimethiconecopolyol, lauramide DEA, cocamide DEA, cocamide MEA, oleyl betaine,cocamidopropyl betaine, cocamidopropyl phosphatidyl PG-dimoniumchloride, dicetyl phosphate (dihexadecyl phosphate), ceteareth-10phosphate, methylbenzethonium chloride, dicetyl phosphate, ceteth-10phosphate (ceteth-10 is the polyethylene glycol ether of cetyl alcoholwhere n has an average value of 10; ceteth-10 phosphate is a mixture ofphosphoric acid esters of ceteth-10), ceteth-20, Brij S10 (polyethyleneglycol octadecyl ether, average M_(n)˜711), Poloxamers (including, butnot limited to, Poloxamer 188(HO(C₂H₄O)_(a)(CH(CH₃)CH₂O)_(b)(C₂H₄O)_(a)H, average molecular weight8400) and Poloxamer 407 (HO(C₂H₄O)_(a)(CH(CH₃)CH₂O)_(b)(C₂H₄O)_(a)H,wherein a is about 101 and b is about 56)), behentrimoniummethosulfate-cetearyl alcohol, emulsifying wax, polyoxyethylene oleylether, PEG-40 stearate, cetostearyl alcohol (cetearyl alcohol),ceteareth-12, ceteareth-20, ceteareth-30, ceteareth alcohol, Ceteth-20(Ceteth-20 is the polyethylene glycol ether of cetyl alcohol where n hasan average value of 20), oleic acid, oleyl alcohol, glyceryl stearate,PEG-75 stearate, PEG-100 stearate, PEG-100 stearate, ceramide 2,ceramide 3, stearic acid, cholesterol, steareth-2, steareth-20,stearamidopropyl dimethylamine, and behentrimonium methosulfate, andcombinations/mixtures thereof.

In certain embodiments, the invention relates to any one of theaforementioned formulations, wherein the third surfactant is selectedfrom the group consisting of: cetyl alcohol, Ceteth-20 (Ceteth-20 is thepolyethylene glycol ether of cetyl alcohol where n has an average valueof 20), PEG-75 stearate, glyceryl stearate, steareth-20, andcombinations/mixtures thereof.

In certain embodiments, the invention relates to any one of theaforementioned formulations, wherein the third surfactant is present inan amount from about 2.5% to about 7.5% by weight of the formulation. Incertain embodiments, the third surfactant is present in an amount fromabout 3% to about 7% by weight of the formulation. In certainembodiments, the third surfactant is present in an amount of about 3%,about 4%, about 5%, about 6%, or about 7%, by weight of the formulation.

In certain embodiments, the invention relates to any one of theaforementioned formulations, wherein the moisturizer or emollient isselected from the group consisting of panthenol, petrolatum, lacticacid, glycerol, butylene glycol, sodium PCA, sodium hyaluronate,Carbowax 200, Carbowax 400, Carbowax 800, cetyl palmitate, PPG-15stearyl ether, lanolin alcohol, lanolin, lanolin derivatives,cholesterol, isostearyl neopentanoate, octyl stearate, mineral oil,isocetyl stearate, myristyl myristate, octyl dodecanol, 2-ethylhexylpalmitate, dimethicone, dimethicone/divinyldimethicone/silsesquioxancecross polymer, polydimethylsiloxane, caprylic/capric triglyceride, sheabutter, jojoba wax, sunflower wax, mimosa wax, phenyl trimethicone,cyclomethicone, C₁₂-C₁₅ alkyl benzoates, C₁₂-C₁₅ alkyl ethylhexanoates,dimethiconol, propylene glycol, Theobroma grandiflorum seed butter,ceramide 2, hydroxypropyl bispalmitamide MEA, hydroxypropyl bislauramideMEA, hydroxypropyl bisisostearamide MEA,1,3-bis(N-2-(hydroxyethyl)stearoylamino)-2-hydroxy propane,bis-hydroxyethyl tocopherylsuccinoylamido hydroxypropane, urea, aloe,allantoin, glycyrrhetinic acid, safflower oil, oleyl alcohol, stearicacid, dicaprylate/dicaprate, diethyl sebacate, isostearyl alcohol,pentylene glycol,1,3-bis(N-2-(hydroxyethyl)palmitoylamino)-2-hydroxypropane, hydrolyzedrice extract, cetyl alcohol, dipalmitoyl hydroxyproline, isononylisononanoate, and combinations/mixtures thereof.

In certain embodiments, the invention relates to any one of theaforementioned formulations, wherein the moisturizer or emollient isselected from the group consisting of panthenol, glycerol, butyleneglycol, sodium hyaluronate,dimethicone/divinyldimethicone/silsesquioxance cross polymer,polydimethylsiloxane, caprylic/capric triglyceride, shea butter, jojobawax, sunflower wax, mimosa wax, C₁₂-C₁₅ alkyl ethylhexanoates,allantoin, pentylene glycol, hydrolyzed rice extract, cetyl alcohol,dipalmitoyl hydroxyproline, isononyl isononanoate, andcombinations/mixtures thereof.

In certain embodiments, the invention relates to any one of theaforementioned formulations, wherein the moisturizer or emollient ispresent in an amount from about 12% to about 38% by weight of theformulation. In certain embodiments, the moisturizer or emollient ispresent in an amount from about 15% to about 35% by weight of theformulation. In certain embodiments, the moisturizer or emollient ispresent in an amount of about 15%, about 16%, about 17%, about 18%,about 19%, about 20%, about 21%, about 22%, about 23%, about 24%, about25%, about 26%, about 27%, about 28%, about 29%, about 30%, about 31%,about 32%, about 33%, about 34%, or about 35% by weight of theformulation.

In certain embodiments, the invention relates to any one of theaforementioned formulations, wherein the moisturizer or emollientcomprises isononyl isononanoate in an amount from about 2% to about 9%by weight of the formulation. In certain embodiments, the inventionrelates to any one of the aforementioned formulations, wherein themoisturizer or emollient comprises isononyl isononanoate in about 2%,about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, or about 9%by weight of the formulation.

In certain embodiments, the invention relates to any one of theaforementioned formulations, wherein the moisturizer or emollientcomprises pentylene glycol in an amount from about 0.1% to about 0.4% byweight of the formulation. In certain embodiments, the invention relatesto any one of the aforementioned formulations, wherein the moisturizeror emollient comprises pentylene glycol in about 0.1%, about 0.2%, about0.3%, or about 0.4% by weight of the formulation.

In certain embodiments, the invention relates to any one of theaforementioned formulations, wherein the moisturizer or emollientcomprises C₁₂-C₁₅ alkyl ethylhexanoates in an amount from about 1% toabout 6% by weight of the formulation. In certain embodiments, theinvention relates to any one of the aforementioned formulations, whereinthe moisturizer or emollient comprises C₁₂-C₁₅ alkyl ethylhexanoates inabout 1%, about 1.5%, about 2%, about 2.5%, about 3%, about 3.5%, about4%, about 4.5%, about 5%, about 5.5%, or about 6% by weight of theformulation.

In certain embodiments, the invention relates to any one of theaforementioned formulations, wherein the moisturizer or emollientcomprises jojoba wax, sunflower wax, and mimosa wax, taken together, inan amount from about 1% to about 3% by weight of the formulation. Incertain embodiments, the invention relates to any one of theaforementioned formulations, wherein the moisturizer or emollientcomprises jojoba wax, sunflower wax, and mimosa wax, taken together, inabout 1%, about 1.5%, about 2%, about 2.5%, or about 3% by weight of theformulation.

In certain embodiments, the invention relates to any one of theaforementioned formulations, wherein the moisturizer or emollientcomprises shea butter in an amount from about 1% to about 3% by weightof the formulation. In certain embodiments, the invention relates to anyone of the aforementioned formulations, wherein the moisturizer oremollient comprises shea butter in about 1%, about 2%, or about 3% byweight of the formulation.

In certain embodiments, the invention relates to any one of theaforementioned formulations, wherein the moisturizer or emollientcomprises caprylic/capric triglyceride in an amount from about 1% toabout 3% by weight of the formulation. In certain embodiments, theinvention relates to any one of the aforementioned formulations, whereinthe moisturizer or emollient comprises caprylic/capric triglyceride inabout 1%, about 2%, or about 3% by weight of the formulation.

In certain embodiments, the invention relates to any one of theaforementioned formulations, wherein the moisturizer or emollientcomprises polydimethylsiloxane in an amount from about 1% to about 3% byweight of the formulation. In certain embodiments, the invention relatesto any one of the aforementioned formulations, wherein the moisturizeror emollient comprises polydimethylsiloxane in about 1%, about 2%, orabout 3% by weight of the formulation.

In certain embodiments, the invention relates to any one of theaforementioned formulations, wherein the moisturizer or emollientcomprises dimethicone/divinyldimethicone/silsesquioxane cross polymer inan amount from about 1% to about 3% by weight of the formulation. Incertain embodiments, the invention relates to any one of theaforementioned formulations, wherein the moisturizer or emollientcomprises dimethicone/divinyldimethicone/silsesquioxane cross polymer inabout 1%, about 2%, or about 3% by weight of the formulation.

In certain embodiments, the invention relates to any one of theaforementioned formulations, wherein the moisturizer or emollientcomprises dipalmitoyl hydroxyproline in an amount from about 0.5% toabout 1.5% by weight of the formulation. In certain embodiments, theinvention relates to any one of the aforementioned formulations, whereinthe moisturizer or emollient comprises dipalmitoyl hydroxyproline inabout 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%, about 1.0%,about 1.1%, about 1.2%, about 1.3%, about 1.4%, or about 1.5% by weightof the formulation.

In certain embodiments, the invention relates to any one of theaforementioned formulations, wherein the moisturizer or emollientcomprises cetyl alcohol in an amount from about 0.5% to about 2.2% byweight of the formulation. In certain embodiments, the invention relatesto any one of the aforementioned formulations, wherein the moisturizeror emollient comprises cetyl alcohol in about 0.5%, about 0.6%, about0.7%, about 0.8%, about 0.9%, about 1.0%, about 1.1%, about 1.2%, about1.3%, about 1.4%, about 1.5%, about 1.6%, about 1.7%, about 1.8%, about1.9%, about 2.0%, about 2.1%, or about 2.2% by weight of theformulation.

In certain embodiments, the invention relates to any one of theaforementioned formulations, wherein the moisturizer or emollientcomprises sodium hyaluronates in an amount from about 0.005% to about0.02% by weight of the formulation. In certain embodiments, theinvention relates to any one of the aforementioned formulations, whereinthe moisturizer or emollient comprises sodium hyaluronates in about0.005%, about 0.01%, about 0.015%, or about 0.02% by weight of theformulation.

In certain embodiments, the invention relates to any one of theaforementioned formulations, wherein the moisturizer or emollientcomprises panthenol in an amount from about 0.5% to about 1.5% by weightof the formulation. In certain embodiments, the invention relates to anyone of the aforementioned formulations, wherein the moisturizer oremollient comprises panthenol in about 0.5%, about 1.0%, or about 1.5%by weight of the formulation.

In certain embodiments, the invention relates to any one of theaforementioned formulations, wherein the moisturizer or emollientcomprises butylene glycol and hydrolyzed rice extract, taken together,in an amount from about 0.5% to about 1.5% by weight of the formulation.In certain embodiments, the invention relates to any one of theaforementioned formulations, wherein the moisturizer or emollientcomprises butylene glycol and hydrolyzed rice extract, taken together,in about 0.5%, about 1.0%, or about 1.5% by weight of the formulation.

In certain embodiments, the invention relates to any one of theaforementioned formulations, wherein the moisturizer or emollientcomprises allantoin in an amount from about 0.2% to about 0.6% by weightof the formulation. In certain embodiments, the invention relates to anyone of the aforementioned formulations, wherein the moisturizer oremollient comprises allantoin in about 0.2%, about 0.3%, about 0.4%,about 0.5%, or about 0.6% by weight of the formulation.

In certain embodiments, the invention relates to any one of theaforementioned formulations, wherein the antioxidant or preservative isselected from the group consisting of imidazolidinyl urea, diazolidinylurea, phenoxyethanol, sodium methyl paraben, methylparaben,ethylparaben, propylparaben, potassium sorbate, sodium benzoate, sorbicacid, benzoic acid, formaldehyde, citric acid, sodium citrate, chlorinedioxide, benzalkonium chloride, benzethonium chloride, cetrimide,dequalinium chloride, cetylpyridinium chloride, phenylmercuric nitrate,phenylmercuric acetate, thimerosal, piroctone olamine, Vitis viniferaseed oil, chlorobutanol, dichlorobenzyl alcohol, phenylethyl alcohol,benzyl alcohol, ascorbic acid and its esters, sodium bisulfite,butylated hydroxytoluene, butylated hydroxyanisole, tocopherol,tocopheryl acetate, sodium ascorbate/ascorbic acid, ascorbyl palmitate,propyl gallate, disodium EDTA, citric acid, sodium citrate, and(3-(4-chlorophenoyx)-2-hydroxypropyl)carbamate, andcombinations/mixtures thereof.

In certain embodiments, the invention relates to any one of theaforementioned formulations, wherein the antioxidant or preservative isselected from the group consisting of potassium sorbate, sodiumbenzoate, butylated hydroxytoluene, tocopherol, tocopheryl acetate,sodium ascorbate, disodium EDTA, and(3-(4-chlorophenoyx)-2-hydroxypropyl)carbamate, andcombinations/mixtures thereof.

In certain embodiments, the invention relates to any one of theaforementioned formulations, wherein the antioxidant or preservative ispresent in an amount from about 0.8% to about 2.5% by weight of theformulation. In certain embodiments, the antioxidant or preservative ispresent in an amount of about 0.8%, about 0.9%, about 1.0%, about 1.1%,about 1.2%, about 1.3%, about 1.4%, about 1.5%, about 1.6%, about 1.7%,about 1.8%, about 1.9%, about 2.0%, about 2.1%, about 2.2%, about 2.3%,about 2.4% or about 2.5% by weight of the formulation.

In certain embodiments, the invention relates to any one of theaforementioned formulations, wherein the antioxidant or preservativecomprises tocopheryl acetate in an amount from about 0.25% to about0.75% by weight of the formulation. In certain embodiments, theinvention relates to any one of the aforementioned formulations, whereinthe antioxidant or preservative comprises tocopheryl acetate in about0.25%, about 0.30%, about 0.35%, about 0.40%, about 0.45%, about 0.50%,about 0.55%, about 0.60%, about 0.65%, about 0.70%, or about 0.75% byweight of the formulation.

In certain embodiments, the invention relates to any one of theaforementioned formulations, wherein the antioxidant or preservativecomprises (3-(4-chlorophenoxy)-2-hydroxypropyl)carbamate in an amountfrom about 0.15% to about 0.45% by weight of the formulation. In certainembodiments, the invention relates to any one of the aforementionedformulations, wherein the antioxidant or preservative comprises(3-(4-chlorophenoxy)-2-hydroxypropyl)carbamate in about 0.15%, about0.20%, about 0.25%, about 0.30%, about 0.35%, about 0.40%, or about0.45% by weight of the formulation.

In certain embodiments, the invention relates to any one of theaforementioned formulations, wherein the antioxidant or preservativecomprises sodium ascorbate in an amount from about 0.1% to about 0.4% byweight of the formulation. In certain embodiments, the invention relatesto any one of the aforementioned formulations, wherein the antioxidantor preservative comprises sodium ascorbate in about 0.10%, about 0.15%,about 0.20%, about 0.25%, about 0.30%, about 0.35%, or about 0.40% byweight of the formulation.

In certain embodiments, the invention relates to any one of theaforementioned formulations, wherein the antioxidant or preservativecomprises tocopherol in an amount from about 0.05% to about 0.25% byweight of the formulation. In certain embodiments, the invention relatesto any one of the aforementioned formulations, wherein the antioxidantor preservative comprises tocopherol in about 0.10%, about 0.15%, orabout 0.20% by weight of the formulation.

In certain embodiments, the invention relates to any one of theaforementioned formulations, wherein the antioxidant or preservativecomprises potassium sorbate in an amount from about 0.05% to about 0.25%by weight of the formulation. In certain embodiments, the inventionrelates to any one of the aforementioned formulations, wherein theantioxidant or preservative comprises potassium sorbate in about 0.10%,about 0.15%, or about 0.20% by weight of the formulation.

In certain embodiments, the invention relates to any one of theaforementioned formulations, wherein the antioxidant or preservativecomprises sodium benzoate in an amount from about 0.05% to about 0.25%by weight of the formulation. In certain embodiments, the inventionrelates to any one of the aforementioned formulations, wherein theantioxidant or preservative comprises sodium benzoate in about 0.10%,about 0.15%, or about 0.20% by weight of the formulation.

In certain embodiments, the invention relates to any one of theaforementioned formulations, wherein the antioxidant or preservativecomprises butylated hydroxytoluene in an amount from about 0.05% toabout 0.15% by weight of the formulation. In certain embodiments, theinvention relates to any one of the aforementioned formulations, whereinthe antioxidant or preservative comprises butylated hydroxytoluene inabout 0.05%, about 0.07%, about 0.09%, about 0.11%, about 0.13%, orabout 0.15% by weight of the formulation.

In certain embodiments, the invention relates to any one of theaforementioned formulations, wherein the antioxidant or preservativecomprises disodium EDTA in an amount from about 0.05% to about 0.15% byweight of the formulation. In certain embodiments, the invention relatesto any one of the aforementioned formulations, wherein the antioxidantor preservative comprises disodium EDTA in about 0.05%, about 0.07%,about 0.09%, about 0.11%, about 0.13%, or about 0.15% by weight of theformulation.

In certain embodiments, the invention relates to any one of theaforementioned formulations, wherein the viscosity modifying agent isselected from the group consisting of hydroxyethylcellulose, xanthangum, sclerotium gum, magnesium aluminum silicate, silica,microcrystalline wax, beeswax, paraffin, and cetyl palmitate andcombinations/mixtures thereof.

In certain embodiments, the invention relates to any one of theaforementioned formulations, wherein the viscosity modifying agent isselected from the group consisting of xanthan gum magnesium aluminumsilicate and combinations/mixtures thereof.

In certain embodiments, the invention relates to any one of theaforementioned formulations, wherein the viscosity modifying agent ispresent in an amount from about 0.3% to about 2.6% by weight of theformulation. In certain embodiments, the invention relates to any one ofthe aforementioned formulations, wherein the viscosity modifying agentis present in about 0.3%, about 0.4%, about 0.5%, about 0.6%, about0.7%, about 0.8%, about 0.9%, about 1.0%, about 1.2%, about 1.4%, about1.6%, about 1.8%, about 2.0%, about 2.2%, about 2.4%, or about 2.6% byweight of the formulation.

In certain embodiments, the invention relates to any one of theaforementioned formulations, wherein the viscosity modifying agentcomprises magnesium aluminum silicate; and the magnesium aluminumsilicate is present in an amount from about 0.3% to about 2.3% by weightof the formulation. In certain embodiments, the magnesium aluminumsilicate is present in about 0.3%, about 0.4%, about 0.5%, about 0.6%,about 0.7%, about 0.8%, about 0.9%, about 1.0%, about 1.1%, about 1.2%,about 1.3%, about 1.4%, about 1.5%, about 1.6%, about 1.7%, about 1.8%,about 1.9%, about 2.0%, about 2.1%, about 2.2%, or about 2.3% by weightof the formulation.

In certain embodiments, the invention relates to any one of theaforementioned formulations, wherein the viscosity modifying agentcomprises xanthan gum; and the xanthan gum is present in an amount fromabout 0.05% to about 0.3% by weight of the formulation. In certainembodiments, the xanthan gum is present in about 0.05%, about 0.1%,about 0.15%, about 0.2%, about 0.25%, or about 0.3% by weight of theformulation.

In certain embodiments, the invention relates to any one of theaforementioned formulations, wherein the pH adjuster is selected fromthe group consisting of citric acid, sodium hydroxide, and sodiumphosphate.

In certain embodiments, the invention relates to any one of theaforementioned formulations, wherein the pH adjuster is sodiumhydroxide.

In certain embodiments, the pH adjuster is added to the formulation as asolution. In certain embodiments, the pH adjuster is added to theformulation as a 50% solution.

In certain embodiments, the invention relates to any one of theaforementioned formulations, wherein the pH adjuster is present in anamount from about 0.02% to about 0.06% by weight of the formulation. Incertain embodiments, the invention relates to any one of theaforementioned formulations, wherein the pH adjuster is present in anamount from about 0.03% to about 0.05% by weight of the formulation. Incertain embodiments, the invention relates to any one of theaforementioned formulations, wherein the pH adjuster is present in about0.02%, about 0.03%, about 0.04%, about 0.05%, or about 0.06% by weightof the formulation.

In certain embodiments, the invention relates to any one of theaforementioned formulations, wherein the sodium hydroxide is present inan amount from about 0.02% to about 0.06% by weight of the formulation.In certain embodiments, the invention relates to any one of theaforementioned formulations, wherein the sodium hydroxide is present inan amount from about 0.03% to about 0.05% by weight of the formulation.In certain embodiments, the invention relates to any one of theaforementioned formulations, wherein the sodium hydroxide is present inabout 0.02%, about 0.03%, about 0.04%, about 0.05%, or about 0.06% byweight of the formulation.

In certain embodiments, the invention relates to any one of theaforementioned formulations, wherein the formulation further comprisesan additional constituent. In certain embodiments, the additionalconstituent is selected from the group consisting of skin protectants,adsorbents, demulcents, emollients, moisturizers, sustained releasematerials, solubilizing agents, skin-penetration agents, skin soothingagents, deodorant agents, antiperspirants, sun screening agents, sunlesstanning agents, vitamins, hair conditioning agents, anti-irritants,anti-aging agents, abrasives, absorbents, anti-caking agents,anti-static agents, astringents, binders/excipients, buffering agents,chelating agents, film forming agents, conditioning agents, opacifyingagents, lipids, anti-inflammatory agents, and immunomodulators, andcombinations thereof.

In certain embodiments, the additional constituent is selected from thegroup consisting of palmitoyl dipeptide-5 diaminobutyloylhydroxythreonine and palmitoyl dipeptide-6 diaminohydroxybutyrate, andcombinations thereof. In certain embodiments, the palmitoyl dipeptide-5diaminobutyloyl hydroxythreonine and palmitoyl dipeptide-6diaminohydroxybutyrate are combined with glycerin. In certainembodiments, the palmitoyl dipeptide-5 diaminobutyloyl hydroxythreonine,palmitoyl dipeptide-6 diaminohydroxybutyrate, and glycerin, takentogether, are present in from about 0.5% to about 1.5% by weight of theformulation. In certain embodiments, the palmitoyl dipeptide-5diaminobutyloyl hydroxythreonine, palmitoyl dipeptide-6diaminohydroxybutyrate, and glycerin, taken together, are present inabout 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%, about 1.0%,about 1.1%, about 1.2%, about 1.3%, about 1.4%, or about 1.5% by weightof the formulation.

In certain embodiments, the additional constituent is algae extract andmugwort extract.

In certain embodiments, the algae extract and mugwort extract, takentogether, are present in from about 0.5% to about 1.5% by weight of theformulation. In certain embodiments, algae extract and mugwort extract,taken together, are present in about 0.5%, about 0.6%, about 0.7%, about0.8%, about 0.9%, about 1.0%, about

In certain embodiments, the additional constituent is stearylglycyrrhetinate. In certain embodiments, the stearyl glycyrrhetinate ispresent in an amount from about 0.05% to about 0.15% by weight of theformulation. In certain embodiments, the stearyl glycyrrhetinate ispresent in about 0.05%, about 0.06%, about 0.07%, about 0.08%, about0.09%, about 0.10%, about 0.11%, about 0.12%, about 0.13%, about 0.14%,or about 0.15% by weight of the formulation.

In certain embodiments, the additional constituent is bisabolol. Incertain embodiments, the bisabolol is present in an amount from about0.1% to about 0.3% by weight of the formulation. In certain embodiments,the bisabolol is present in about 0.1%, about 0.15%, about 0.2%, about0.25%, or about 0.3% by weight of the formulation.

In certain embodiments, the additional constituent is bergamot. Incertain embodiments, the bergamot is present in an amount from about0.15% to about 0.45% by weight of the formulation. In certainembodiments, the bergamot is present in about 0.15%, about 0.2%, about0.25%, about 0.3%, about 0.35%, about 0.4%, or about 0.45% by weight ofthe formulation.

In certain embodiments, the additional constituent is tetrahexyldecylascorbate. In certain embodiments, the tetrahexyldecyl ascorbate ispresent in an amount from about 0.25% to about 0.75% by weight of theformulation. In certain embodiments, the tetrahexyldecyl ascorbate ispresent in about 0.25%, about 0.3%, about 0.35%, about 0.4%, about0.45%, about 0.5%, about 0.55%, about 0.6%, about 0.65%, about 0.7%, orabout 0.75% by weight of the formulation.

In certain embodiments, the additional constituent ispalmitoyl-lysyl-valyl-lysine bistrifluoroacetate. In certainembodiments, the palmitoyl-lysyl-valyl-lysine bistrifluoroacetate iscombined with glycerin. In certain embodiments, thepalmitoyl-lysyl-valyl-lysine bistrifluoroacetate and glycerin, takentogether, are present in an amount from about 1% to about 4% by weightof the formulation. In certain embodiments, thepalmitoyl-lysyl-valyl-lysine bistrifluoroacetate and glycerin, takentogether, are present in about 1%, about 1.5%, about 2%, about 2.5%,about 3%, about 3.5%, or about 4% by weight of the formulation.

In certain embodiments, the additional constituent is niacinamide. Incertain embodiments, the niacinamide is present in an amount from about0.5% to about 1.5% by weight of the formulation. In certain embodiments,the niacinamide is present in about 0.5%, about 0.6%, about 0.7%, about0.8%, about 0.9%, about 1.0%, about 1.1%, about 1.2%, about 1.3%, about1.4%, or about 1.5% by weight of the formulation.

Exemplary Foam-Forming Compositions of the Invention

In certain embodiments, the invention relates to a foam-formingcomposition, comprising: any one of the aforementioned formulations; anda propellant.

In certain embodiments, the invention relates to a foam-formingcomposition, consisting essentially of: any one of the aforementionedformulations; and a propellant.

In certain embodiments, the invention relates to a foam-formingcomposition, consisting of: any one of the aforementioned formulations;and a propellant.

In certain embodiments, the invention relates to a foam-formingcomposition, comprising: any one of the aforementioned formulations; apropellant; and a purge gas.

In certain embodiments, the invention relates to a foam-formingcomposition, consisting essentially of: any one of the aforementionedformulations; a propellant; and a purge gas.

In certain embodiments, the invention relates to a foam-formingcomposition, consisting of: any one of the aforementioned formulations;a propellant; and a purge gas.

Exemplary Propellants

As outlined above, in certain embodiments, the invention relates to afoam-forming composition comprising a formulation, a propellant, and apurge gas. The propellants described below may be present in any one ofthe aforementioned foam-forming compositions.

In certain embodiments, the invention relates to any one of theaforementioned foam-forming compositions, wherein the propellant isselected from the group consisting of 1,1,1,2-tetrafluoroethane,1,1,1,2,3,3,3-heptafluoropropane, 1,3,3,3-tetrafluoropropene, andcombinations/mixtures thereof.

In certain embodiments, the invention relates to any one of theaforementioned foam-forming compositions, wherein the propellant ispresent in an amount from about 2% to about 50% by weight of thefoam-forming composition. In certain embodiments, the invention relatesto any one of the aforementioned foam-forming compositions, wherein thepropellant is present in an amount from about 5% to about 30% by weightof the foam-forming composition. In certain embodiments, the inventionrelates to any one of the aforementioned foam-forming compositions,wherein the propellant is about 5%, about 6%, about 7%, about 8%, about9%, about 10%, about 11%, about 12%, about 13%, about 14%, about 15%,about 16%, about 17%, about 18%, about 19%, about 20%, about 21%, about22%, about 23%, about 24%, about 25%, about 26%, about 27%, about 28%,about 29%, or about 30% by weight of the foam-forming composition.

Exemplary Purge Gases

As outlined above, in certain embodiments, the invention relates to afoam-forming composition comprising a formulation, a propellant, and apurge gas. The purge gases described below may be present in any one ofthe aforementioned foam-forming compositions.

In certain embodiments, the invention relates to any one of theaforementioned compositions, wherein the purge gas is selected from thegroup consisting of nitrogen and argon.

In certain embodiments, the invention relates to any one of theaforementioned compositions, wherein the purge gas is argon.

In certain embodiments, the invention relates to any one of theaforementioned compositions, wherein the purge gas is present in anamount from about 0.4% to about 6% by weight of the composition. Incertain embodiments, the invention relates to any one of theaforementioned compositions, wherein the purge gas is present in anamount from about 0.8% to about 5% by weight of the composition. Incertain embodiments, the invention relates to any one of theaforementioned compositions, wherein the purge gas is about 0.8%, about1%, about 1.2%, about 1.4%, about 1.6%, about 1.8%, about 2%, about2.2%, about 2.5%, about 2.6%, about 2.8%, about 3%, about 3.2%, about3.4%, about 3.6%, about 3.8%, about 4%, about 4.2%, about 4.4%, about4.6%, about 4.8% or about 5% by weight of the composition.

Exemplary Properties of Formulations of the Invention

In certain embodiments, the invention relates to any one of theaforementioned formulations, wherein the formulation is semi-solid.

In certain embodiments, the invention relates to any one of theaforementioned formulations, wherein the formulation is a cream.

In certain embodiments, the invention relates to any one of theaforementioned formulations, wherein the formulation is a gel.

In certain embodiments, the invention relates to any one of theaforementioned formulations that, upon expulsion from an aerosolcontainer, forms a foam. In certain embodiments, the foam istemperature-stable. In certain embodiments, the foam is time-stable. Incertain embodiments, the density of the foam is from about 0.05 to about0.5 g/cm³. In certain embodiments, the invention relates to any one ofthe aforementioned formulations that is easily shaken in an aerosolcontainer. In certain embodiments, the invention relates to any one ofthe aforementioned formulations that is easily dispensed from an aerosolcontainer.

In certain embodiments, the invention relates to any one of theaforementioned formulations that, upon application to the skin of anaffected subject, is non-irritating.

In certain embodiments, the invention relates to any one of theaforementioned formulations that, upon application to the skin of anaffected subject, is well-tolerated.

In certain embodiments, the invention relates to any one of theaforementioned formulations that, upon application to the skin of anaffected subject, reduces inflammation.

In certain embodiments, the invention relates to any one of theaforementioned formulations that, upon application to the skin of anaffected subject, is non-cytotoxic.

In certain embodiments, the invention relates to any one of theaforementioned formulations that, upon application to the skin of anaffected subject, is weakly sensitizing. In certain embodiments, theinvention relates to any one of the aforementioned formulations that,upon application to the skin of an affected subject, is non-sensitizing.

In certain embodiments, the invention relates to any one of theaforementioned formulations that, upon application to the skin of anaffected subject, does not produce edema or erythema.

In certain embodiments, the invention relates to any one of theaforementioned formulations that, upon application to the skin of anaffected subject, moisturizes the skin.

In certain embodiments, the invention relates to any one of theaforementioned formulations that, upon application to the skin of anaffected subject, increases hydration of the skin.

In certain embodiments, the invention relates to any one of theaforementioned formulations that, upon application to the skin of anaffected subject, reduces transepidermal water loss.

Exemplary Formulations of the Invention for Particular Uses

In certain embodiments, the invention relates to any one of theformulations for use in the treatment or prevention of a skin disorder.

In certain embodiments, the invention relates to any one of theaforementioned formulations for use in the treatment or prevention of askin disorder, wherein the emulsion or composition is formulated fortopical application once daily or twice daily.

In certain embodiments, the skin disorder is acne vulgaris or keratosispilaris.

In certain embodiments, the skin disorder is skin aging. In certainembodiments, the treatment or prevention of skin aging includes thetreatment or prevention of wrinkles, sun spots, dullness, fine lines,increased pore size, or uneven skin tone.

Exemplary Methods of Use

In certain embodiments, the invention relates to a method of treating askin disorder, comprising the step of applying to an affected area of asubject in need thereof a therapeutically-effective amount of any one ofthe aforementioned formulations.

In one embodiment, the present invention relates to any one of theabove-mentioned methods, wherein the subject is human.

In one embodiment, the present invention relates to any one of theabove-mentioned methods, wherein the composition is applied once daily.

In one embodiment, the present invention relates to any one of theabove-mentioned methods, wherein the composition is applied twice daily.

In certain embodiments, the present invention relates to any one of theabove-mentioned methods, wherein the skin disorder is acne vulgaris orkeratosis pilaris.

In certain embodiments, the present invention relates to any one of theabove-mentioned methods, wherein the skin disorder is skin aging. Incertain embodiments, the present invention relates to any one of theabove-mentioned methods, wherein the treatment or prevention of skinaging includes the treatment or prevention of wrinkles, sun spots,dullness, fine lines, increased pore size, or uneven skin tone.

Exemplary Methods of Making Formulations of the Invention

In certain embodiments, the invention relates to a method of making anyone of the aforementioned formulations, comprising the step of

combining any one of the aforementioned active agent-containingmicroemulsions with the a moisturizer or emollient, the thirdsurfactant, the antioxidant or preservative, the viscosity modifyingagent; and the pH adjuster.

In certain embodiments, the invention relates to a method of making anyone of the aforementioned formulations, comprising the steps describedin Example 4.

EXEMPLIFICATION

The invention now being generally described, it will be more readilyunderstood by reference to the following examples which are includedmerely for purposes of illustration of certain aspects and embodimentsof the present invention, and are not intended to limit the invention.

Example 1 Spontaneous Microemulsion Formation by Mixtures of aCaprylocaproyl Polyethylene Glycol-Based Surfactant and Cyclodextrin inAqueous Media

Microemulsion preparation: Any two components (examples:Labrasol®-water, HPXCD-water, or Labrasol®-HPXCD) were mixed (indifferent ratios) in different scintillation vials and then the thirdcomponent was titrated to each vial until a clear-to-turbid orturbid-to-clear transition occurred (in simple situations). Finally wt %percentages data for each component (Labrasol®, water, and cyclodextrin)were plotted to construct the ternary phase diagram. See FIG. 2.

In FIG. 3, the “water” phase (above) was replaced with an “aqueous”phase. An example of an aqueous phase is shown in FIG. 5.

Example 2 Solubility/Dispersibility of Retinol in theLabrasol®-HPGCD-Water Systems And in Labrasol®, HPGCD, and Water,Individually

Materials

Drug used: 1. Solid Retinol (98%) from Sigma, 2. Retistar (5% Retinol,caprylic/capric triglyceride, sodium ascorbate, Tocopherol) from BASF,3. Retinol 50C (50% retinol, ethoxylated sorbitan monolaurate (Tween20), butylated hydroxytoluene (BHT),2-(1,1-dimethylethyl)-4-methoxy-phenol) from BASF.

Cyclodextrin used: hydroxypropyl-X-cyclodextrin (X=alpha, beta, orgamma).

Methods

Vial L from FIG. 4( a) shows the formation of a novel microemulsion(clear transparent system) as well as complete miscibility of Retistar(final retinol concentration: 0.06%) in Labrasol®-HPGCD-watermicroemulsion system (Note: capric/caprylic triglycerides coming fromthe Retistar are also contributing to the microemulsion system). Themiscibility of retinol may be attributed to the drug incorporation inthe cyclodextrin system as well as the micro emulsion system.

Vial labeled 8 from FIG. 4( b) shows the formation of a novelmicroemulsion (clear transparent system) as well as complete miscibilityof Retinol 50C (final retinol concentration: 1.2%) inLabrasol®-HPGCD-water microemulsion system (Note: ethoxylated sorbitanmonolaurate coming from the Retinol 50C are also contributing to themicroemulsion system). The miscibility of Retinol may be attributed tothe drug incorporation in the cyclodextrin system as well as in themicroemulsion system.

Vial labeled 1 from FIG. 4( c) shows the formation of a novelmicroemulsion (clear transparent system) as well as complete miscibilityof solid retinol (final retinol concentration: 1.2%) inLabrasol®-HPGCD-water microemulsion system. This miscibility of retinolmay be attributed to the drug incorporation in the cyclodextrin systemas well as in the microemulsion system

Retinol is incorporated in the cyclodextrin system as well as in themicroemulsion system.

Example 3 Encapsulation of Pharmaceutical/Cosmetic Ingredients inCD-Stabilized Microemulsions

Materials

Retinol used: 1. Solid retinol (98%) from Sigma, 2. Retistar (5%retinol, caprylic/capric triglyceride, sodium ascorbate, tocopherol)from BASF, 3. Retinol 50C (50% retinol, ethoxylated sorbitanmonolaurate, BHT, 2-(1,1-dimethylethyl)-4-methoxy-phenol from BASF

Methods

Microemulsion preparation: Any two components (examples:Labrasol®-water, cyclodextrin-water, or Labrasol®-HPBCD) were mixed (indifferent ratios) in different scintillation vials and then the thirdcomponent was titrated to each vial until a clear-to-turbid orturbid-to-clear transition occurred (in simple situations). Finally wt %percentages data for each component (Labrosol, water, and cyclodextrin)were plotted to construct the ternary phase diagram.

Incorporation of Drug: Drug can be dissolved in the individualcomponents or any of the two-component combination systems, followed bymicroemulsion formulation. Alternatively Drug can be directly added tothe previously prepared microemulsion phase followed by shaking until aclear solution is achieved (when the achievable drug concentration isknown previously).

See FIG. 7.

Example 4 Retinol Cream

A 0.5% retinol cream base was formulated, which was then used for makingan aerosol foam product. The composition is shown in FIG. 10, and themethod of formulation is outlined below.

Stepwise strategies for making a semi-solid formulation using acyclodextrin-based microemulsion that was used to make the 0.5% retinolproduct.

Step 1. Construction of the microemulsion phase diagram replacing waterwith an aqueous phase of the formulation (FIG. 8).

Step 2. Preparation of a microemulsion based on a composition selectedfrom the clear zone of the phase diagram of Labrasol®-HPXCD-aqueoussolution system.

Step 3. Immiscibility/compatibility test: Compatibility between theprepared microemulsion and the liquid oily phase of the targeted creamformulation was tested (FIG. 11). It was observed that the microemulsionremained intact in the presence of oil coming from the oil phase of thecream. This test was repeated using other oils. A desirable oil is onethat does not destabilize the microemulsion.

Step 4. Appropriate procedure was designed to formulate the final creamformulation (refer to FIG. 10). FIG. 12 shows the visual appearance ofthe cyclodextrin-based cream and the corresponding control (withoutmicroemulsion).

Procedure for making the final cream formulation (see FIG. 10):

Phase A:

-   -   1. Weigh all ingredients from Phase A into a glass beaker.    -   2. Heat and mix to 60° C. and hold at 60° C. with continuous        mixing with a spatula. Use a water bath to get uniform heating.

Phase B:

-   -   1. In a beaker add microemulsion system at room temperature    -   2. Place beaker under the homogenizer and while mixing rapidly        sprinkle in Veegum K granules being careful to avoid lumps    -   3. Homogenize phase B for 5 minutes.

Phase C:

-   -   1. At room temperature, weigh phase C ingredients into a beaker    -   2. Mix until all the xanthan gum is fully wetted out and lump        free

Phase D:

-   -   1. Weigh out the ingredients of Phase D into a small beaker and        transfer to Phase BC (see Procedure below) at room temperature

Phase E:

-   -   1. At 45° C. individually add phase E to the batch and mix until        uniform

Phase F:

-   -   1. In a small beaker combine phase F    -   2. Heat and mix phase F to 50° C.    -   3. Mix until all of the chlorphenesin is dissolved

Phase G:

-   -   1. Weigh ingredients into a beaker and thoroughly mix together

Phase H:

-   -   1. Already added as Phase B.

Phase I:

-   -   1. Take out the fragrance from refrigerator and let it come to        room temperature

Procedure:

-   -   1. After Homogenizing Phase B, mix it with Phase C for 15        minutes until fully hydrated on the lightning mixer. Keep an        argon blanket on during the entire batch making process.    -   2. Add Phase D to the above mixture and then heat and mix phase        BCD to 50° C.    -   3. Making sure that phase A is at 60° C. and continuously        mixing, transfer phase A into phase BCD at 50° C.    -   4. Once fully transferred homogenize the batch for 3 minutes    -   5. Then turn off the homogenizer and by using only the lightning        mixer cool the batch to 45° C. (no water bath).    -   6. At 45° C. individually add phase E to the batch and mix until        uniform    -   7. Then add phase F to the batch at 45° C. and mix and cool        batch to 32-30° C. (no water bath)    -   8. Add Phase G to the formulation at 30° C.    -   9. Slowly add fragrance while batch is mixing on lightning mixer        and keep batch covered    -   10. QS batch once it is at 25° C.    -   11. Versate (whip-mix) the entire batch and place in a suitable        container protected from light. Blanket headspace the container        with argon and seal.

INCORPORATION BY REFERENCE

All of the U.S. patents and U.S. published patent applications citedherein are hereby incorporated by reference.

EQUIVALENTS

Those skilled in the art will recognize, or be able to ascertain usingno more than routine experimentation, many equivalents to the specificembodiments of the invention described herein. Such equivalents areintended to be encompassed by the following claims.

We claim:
 1. An active agent-containing microemulsion, consistingessentially of: an active agent and a microemulsion, wherein themicroemulsion consists essentially of an aqueous phase, a firstsurfactant, and a second surfactant; and the first surfactant is acyclodextrin or a derivative of a cyclodextrin.
 2. The activeagent-containing microemulsion of claim 1, wherein the active agentcomprises retinol.
 3. The active agent-containing microemulsion of claim1, wherein the active agent is retinol.
 4. The active agent-containingmicroemulsion of claim 1, wherein the active agent is present in anamount from about 0.01% to about 5% by weight of the activeagent-containing microemulsion.
 5. The active agent-containingmicroemulsion of claim 1, wherein the aqueous phase is present in anamount from about 75% to about 95% by weight of the microemulsion. 6.The active agent-containing microemulsion of claim 1, wherein theaqueous phase comprises a moisturizer or emollient.
 7. The activeagent-containing microemulsion of claim 6, wherein the moisturizer oremollient is selected from the group consisting of panthenol, allantoin,sodium hyaluraonate, pentylene glycol, and combinations/mixturesthereof.
 8. The active agent-containing microemulsion of claim 6,wherein the moisturizer or emollient is present in an amount from about0.8% to about 2.3% by weight of the aqueous phase.
 9. The activeagent-containing microemulsion of claim 1, wherein the aqueous phasecomprises an anti-inflammatory agent.
 10. The active agent-containingmicroemulsion of claim 9, wherein the anti-inflammatory agent isniacinamide.
 11. The active agent-containing microemulsion of claim 9,wherein the anti-inflammatory agent is present in an amount from about0.5% to about 2% by weight of the aqueous phase.
 12. The activeagent-containing microemulsion of claim 1, wherein the aqueous phasecomprises an antioxidant or preservative.
 13. The activeagent-containing microemulsion of claim 12, wherein the antioxidant orpreservative is selected from the group consisting of potassium sorbate,sodium benzoate, disodium EDTA, and combinations/mixtures thereof. 14.The active agent-containing microemulsion of claim 12, wherein theantioxidant or preservative is present in an amount from about 0.2% toabout 0.6% by weight of the aqueous phase.
 15. The activeagent-containing microemulsion of claim 1, wherein the aqueous phasecomprises a pH adjuster.
 16. The active agent-containing microemulsionof claim 15, wherein the pH adjuster is sodium hydroxide.
 17. The activeagent-containing microemulsion of claim 15, wherein the pH adjuster ispresent in an amount from about 0.02% to about 0.1% by weight of theaqueous phase.
 18. The active agent containing microemulsion of claim 1,wherein the first surfactant is present in an amount from about 1% toabout 8% by weight of the microemulsion.
 19. The active agent containingmicroemulsion of claim 1, wherein the first surfactant is hydroxypropylα-cyclodextrin, hydroxypropyl β-cyclodextrin, or hydroxypropylγ-cyclodextrin.
 20. The active agent containing microemulsion of claim1, wherein the first surfactant is hydroxypropyl β-cyclodextrin.
 21. Theactive agent containing microemulsion of claim 1, wherein the secondsurfactant is present in an amount from about 4% to about 22% by weightof the microemulsion.
 22. The active agent containing microemulsion ofclaim 1, wherein the second surfactant is caprylocaproyl macrogol-8glycerides or caprylocaproyl polyoxyl-8 glycerides, or a combinationthereof.
 23. The active agent containing microemulsion of claim 1,wherein the active agent containing microemulsion consists essentiallyof: an active agent and a microemulsion; and the microemulsion consistsessentially of water, in an amount of about 80% by weight of themicroemulsion; hydroxypropyl β-cyclodextrin, in an amount of about 5% byweight of the microemulsion; and caprylocaproyl macrogol-8 glycerides orcaprylocaproyl polyoxyl-8 glycerides, in an amount of about 15% byweight of the microemulsion.
 24. The active agent containingmicroemulsion of claim 1, wherein the active agent containingmicroemulsion consists essentially of: an active agent and amicroemulsion; and the microemulsion consists essentially of water, inan amount of about 90% by weight of the microemulsion; hydroxypropylβ-cyclodextrin, in an amount of about 3% by weight of the microemulsion;and caprylocaproyl macrogol-8 glycerides or caprylocaproyl polyoxyl-8glycerides, in an amount of about 7% by weight of the microemulsion.